Immunology of human fibrosis.
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
16
04
2023
accepted:
08
06
2023
medline:
28
8
2023
pubmed:
21
7
2023
entrez:
20
7
2023
Statut:
ppublish
Résumé
Fibrosis, defined by the excess deposition of structural and matricellular proteins in the extracellular space, underlies tissue dysfunction in multiple chronic diseases. Approved antifibrotics have proven modest in efficacy, and the immune compartment remains, for the most part, an untapped therapeutic opportunity. Recent single-cell analyses have interrogated human fibrotic tissues, including immune cells. These studies have revealed a conserved profile of scar-associated macrophages, which localize to the fibrotic niche and interact with mesenchymal cells that produce pathological extracellular matrix. Here we review recent advances in the understanding of the fibrotic microenvironment in human diseases, with a focus on immune cell profiles and functional immune-stromal interactions. We also discuss the key role of the immune system in mediating fibrosis regression and highlight avenues for future study to elucidate potential approaches to targeting inflammatory cells in fibrotic disorders.
Identifiants
pubmed: 37474654
doi: 10.1038/s41590-023-01551-9
pii: 10.1038/s41590-023-01551-9
doi:
Types de publication
Journal Article
Review
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1423-1433Subventions
Organisme : Medical Research Council
ID : MR/W015919/1
Pays : United Kingdom
Informations de copyright
© 2023. Springer Nature America, Inc.
Références
Wynn, T. A. Fibrotic disease and the T
pubmed: 15286725
pmcid: 2702150
doi: 10.1038/nri1412
Taylor, R. S. et al. Association between fibrosis stage and outcomes of patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis. Gastroenterology 158, 1611–1625 (2020).
pubmed: 32027911
doi: 10.1053/j.gastro.2020.01.043
Moon, A. M., Singal, A. G. & Tapper, E. B. Contemporary epidemiology of chronic liver disease and cirrhosis. Clin. Gastroenterol. Hepatol. 18, 2650–2666 (2020).
pubmed: 31401364
doi: 10.1016/j.cgh.2019.07.060
Ramachandran, P. et al. Resolving the fibrotic niche of human liver cirrhosis at single-cell level. Nature 575, 512–518 (2019). scRNA-seq study of healthy versus fibrotic human liver, defining the transcriptional profile of SAMacs and studying ligand–receptor interactions in the fibrotic niche.
pubmed: 31597160
pmcid: 6876711
doi: 10.1038/s41586-019-1631-3
Buonomo, E. L. et al. Liver stromal cells restrict macrophage maturation and stromal IL-6 limits the differentiation of cirrhosis-linked macrophages. J. Hepatol. 76, 1127–1137 (2022).
pubmed: 35074474
doi: 10.1016/j.jhep.2021.12.036
Hendrikx, T. et al. Soluble TREM2 levels reflect the recruitment and expansion of TREM2
pubmed: 35750138
doi: 10.1016/j.jhep.2022.06.004
Remmerie, A. et al. Osteopontin expression identifies a subset of recruited macrophages distinct from kupffer cells in the fatty liver. Immunity 53, 641–657 (2020).
pubmed: 32888418
pmcid: 7501731
doi: 10.1016/j.immuni.2020.08.004
Xiong, X. et al. Landscape of intercellular crosstalk in healthy and NASH liver revealed by single-cell secretome gene analysis. Mol. Cell 75, 644–660 (2019).
pubmed: 31398325
pmcid: 7262680
doi: 10.1016/j.molcel.2019.07.028
Daemen, S. et al. Dynamic shifts in the composition of resident and recruited macrophages influence tissue remodeling in NASH. Cell Rep. 34, 108626 (2021).
pubmed: 33440159
pmcid: 7877246
doi: 10.1016/j.celrep.2020.108626
Fabre, T. et al. Identification of a broadly fibrogenic macrophage subset induced by type 3 inflammation. Sci. Immunol. 8, eadd8945 (2023). Integrated analysis of lung and liver scRNA-seq data from human and mouse, defining the conserved features of SAMacs across organs. Highlights the role of GM-CSF, IL-17A and TGFβ in SAMac differentiation.
pubmed: 37027478
doi: 10.1126/sciimmunol.add8945
Guilliams, M. et al. Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches. Cell 185, 379–396 (2022).
pubmed: 35021063
pmcid: 8809252
doi: 10.1016/j.cell.2021.12.018
Govaere, O. et al. Transcriptomic profiling across the nonalcoholic fatty liver disease spectrum reveals gene signatures for steatohepatitis and fibrosis. Sci. Transl. Med. 12, eaba4448 (2020).
pubmed: 33268509
doi: 10.1126/scitranslmed.aba4448
Poch, T. et al. Single-cell atlas of hepatic T cells reveals expansion of liver-resident naive-like CD4
pubmed: 33774059
pmcid: 8310924
doi: 10.1016/j.jhep.2021.03.016
Rau, M. et al. Progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis is marked by a higher frequency of T
pubmed: 26621860
doi: 10.4049/jimmunol.1501175
Meng, F. et al. Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice. Gastroenterology 143, 765–776 (2012).
pubmed: 22687286
doi: 10.1053/j.gastro.2012.05.049
Dudek, M. et al. Auto-aggressive CXCR6
pubmed: 33762736
doi: 10.1038/s41586-021-03233-8
Pallett, L. J. et al. Tissue CD14
pubmed: 36697826
doi: 10.1038/s41586-022-05645-6
Wang, S. et al. An autocrine signaling circuit in hepatic stellate cells underlies advanced fibrosis in nonalcoholic steatohepatitis. Sci. Transl. Med. 15, eadd3949 (2023).
pubmed: 36599008
doi: 10.1126/scitranslmed.add3949
Wallace, S. J., Tacke, F., Schwabe, R. F. & Henderson, N. C. Understanding the cellular interactome of non-alcoholic fatty liver disease. JHEP Rep. 4, 100524 (2022).
pubmed: 35845296
pmcid: 9284456
doi: 10.1016/j.jhepr.2022.100524
Ramachandran, P., Matchett, K. P., Dobie, R., Wilson-Kanamori, J. R. & Henderson, N. C. Single-cell technologies in hepatology: new insights into liver biology and disease pathogenesis. Nat. Rev. Gastroenterol. Hepatol. 17, 457–472 (2020).
pubmed: 32483353
doi: 10.1038/s41575-020-0304-x
Lederer, D. J. & Martinez, F. J. Idiopathic pulmonary fibrosis. N. Engl. J. Med. 378, 1811–1823 (2018).
pubmed: 29742380
doi: 10.1056/NEJMra1705751
Wolters, P. J., Collard, H. R. & Jones, K. D. Pathogenesis of idiopathic pulmonary fibrosis. Annu Rev. Pathol. 9, 157–179 (2014).
pubmed: 24050627
doi: 10.1146/annurev-pathol-012513-104706
Adams, T. S. et al. Single-cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis. Sci. Adv. 6, eaba1983 (2020). scRNA-seq study from human lung fibrosis. A web-based browser of this and other articles is available at http://ipfcellatlas.com
pubmed: 32832599
pmcid: 7439502
doi: 10.1126/sciadv.aba1983
Habermann, A. C. et al. Single-cell RNA sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis. Sci. Adv. 6, eaba1972 (2020). scRNA-seq study from human lung fibrosis. A web-based browser of this and other articles is available at http://ipfcellatlas.com
pubmed: 32832598
pmcid: 7439444
doi: 10.1126/sciadv.aba1972
Reyfman, P. A. et al. Single-cell transcriptomic analysis of human lung provides insights into the pathobiology of pulmonary fibrosis. Am. J. Respir. Crit. Care Med 199, 1517–1536 (2019). scRNA-seq study from human lung fibrosis. A web-based browser of this and other articles is available at http://ipfcellatlas.com
pubmed: 30554520
pmcid: 6580683
doi: 10.1164/rccm.201712-2410OC
Morse, C. et al. Proliferating SPP1/MERTK-expressing macrophages in idiopathic pulmonary fibrosis. Eur. Respir. J. 54, 1802441 (2019). scRNA-seq study from human lung fibrosis. A web-based browser of this and other articles is available at http://ipfcellatlas.com
pubmed: 31221805
pmcid: 8025672
doi: 10.1183/13993003.02441-2018
Aran, D. et al. Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage. Nat. Immunol. 20, 163–172 (2019). Experimental models of lung fibrosis demonstrating the role of monocyte-derived macrophages in the early fibrotic stage after injury.
pubmed: 30643263
pmcid: 6340744
doi: 10.1038/s41590-018-0276-y
Wendisch, D. et al. SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis. Cell 184, 6243–6261 (2021). Analysis of fibrotic changes in COVID-19 lung samples with comparison to IPF.
pubmed: 34914922
pmcid: 8626230
doi: 10.1016/j.cell.2021.11.033
Wu, X. et al. 3-month, 6-month, 9-month, and 12-month respiratory outcomes in patients following COVID-19-related hospitalisation: a prospective study. Lancet Respir. Med 9, 747–754 (2021).
pubmed: 33964245
pmcid: 8099316
doi: 10.1016/S2213-2600(21)00174-0
Faverio, P. et al. One-year pulmonary impairment after severe COVID-19: a prospective, multicenter follow-up study. Respir. Res 23, 65 (2022).
pubmed: 35313890
pmcid: 8934910
doi: 10.1186/s12931-022-01994-y
Leslie, J. et al. FPR-1 is an important regulator of neutrophil recruitment and a tissue-specific driver of pulmonary fibrosis. JCI Insight 5, e125937 (2020).
pubmed: 32102985
pmcid: 7101152
doi: 10.1172/jci.insight.125937
Deng, L., Huang, T. & Zhang, L. T cells in idiopathic pulmonary fibrosis: crucial but controversial. Cell Death Discov. 9, 62 (2023).
pubmed: 36788232
pmcid: 9929223
doi: 10.1038/s41420-023-01344-x
Ichikawa, T. et al. CD103
pubmed: 31591568
doi: 10.1038/s41590-019-0494-y
Chiaramonte, M. G., Donaldson, D. D., Cheever, A. W. & Wynn, T. A. An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response. J. Clin. Invest. 104, 777–785 (1999).
pubmed: 10491413
pmcid: 408441
doi: 10.1172/JCI7325
Fallon, P. G., Richardson, E. J., McKenzie, G. J. & McKenzie, A. N. Schistosome infection of transgenic mice defines distinct and contrasting pathogenic roles for IL-4 and IL-13: IL-13 is a profibrotic agent. J. Immunol. 164, 2585–2591 (2000).
pubmed: 10679097
doi: 10.4049/jimmunol.164.5.2585
Cheever, A. W. et al. Anti-IL-4 treatment of Schistosoma mansoni-infected mice inhibits development of T cells and non-B, non-T cells expressing T
pubmed: 8021510
doi: 10.4049/jimmunol.153.2.753
Raghu, G. et al. SAR156597 in idiopathic pulmonary fibrosis: a phase 2 placebo-controlled study (DRI11772). Eur. Respir. J. 52, 1801130 (2018).
pubmed: 30337444
doi: 10.1183/13993003.01130-2018
Maher, T. M. et al. Phase 2 trial to assess lebrikizumab in patients with idiopathic pulmonary fibrosis. Eur. Respir. J. 57, 1902442 (2021).
pubmed: 33008934
pmcid: 7859504
doi: 10.1183/13993003.02442-2019
Allanore, Y. et al. A randomised, double-blind, placebo-controlled, 24-week, phase II, proof-of-concept study of romilkimab (SAR156597) in early diffuse cutaneous systemic sclerosis. Ann. Rheum. Dis. 79, 1600–1607 (2020).
pubmed: 32963047
doi: 10.1136/annrheumdis-2020-218447
Jha, V. et al. Chronic kidney disease: global dimension and perspectives. Lancet 382, 260–272 (2013).
pubmed: 23727169
doi: 10.1016/S0140-6736(13)60687-X
Li, L., Fu, H. & Liu, Y. The fibrogenic niche in kidney fibrosis: components and mechanisms. Nat. Rev. Nephrol. 18, 545–557 (2022).
pubmed: 35788561
doi: 10.1038/s41581-022-00590-z
Kuppe, C. et al. Decoding myofibroblast origins in human kidney fibrosis. Nature 589, 281–286 (2021). scRNA-seq study of healthy versus fibrotic human kidney, generating a cell atlas and highlighting myeloid–mesenchymal interactions.
Hoeft, K. et al. Platelet-instructed SPP1
pubmed: 36807143
pmcid: 9992450
doi: 10.1016/j.celrep.2023.112131
Conway, B. R. et al. Kidney single-cell atlas reveals myeloid heterogeneity in progression and regression of kidney disease. J. Am. Soc. Nephrol. 31, 2833–2854 (2020).
pubmed: 32978267
pmcid: 7790206
doi: 10.1681/ASN.2020060806
Doke, T. et al. Single-cell analysis identifies the interaction of altered renal tubules with basophils orchestrating kidney fibrosis. Nat. Immunol. 23, 947–959 (2022).
pubmed: 35552540
doi: 10.1038/s41590-022-01200-7
Basile, D. P., Ullah, M. M., Collet, J. A. & Mehrotra, P. T helper 17 cells in the pathophysiology of acute and chronic kidney disease. Kidney Res. Clin. Pract. 40, 12–28 (2021).
pubmed: 33789382
pmcid: 8041630
doi: 10.23876/j.krcp.20.185
Frangogiannis, N. G. Cardiac fibrosis. Cardiovasc Res. 117, 1450–1488 (2021).
pubmed: 33135058
doi: 10.1093/cvr/cvaa324
Miranda, A. M. A. et al. Single-cell transcriptomics for the assessment of cardiac disease. Nat. Rev. Cardiol. 20, 289–308 (2022).
pubmed: 36539452
doi: 10.1038/s41569-022-00805-7
Koenig, A. L. et al. Single-cell transcriptomics reveals cell-type-specific diversification in human heart failure. Nat. Cardiovasc. Res. 1, 263–280 (2022).
pubmed: 35959412
pmcid: 9364913
doi: 10.1038/s44161-022-00028-6
Reichart, D. et al. Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies. Science 377, eabo1984 (2022).
pubmed: 35926050
pmcid: 9528698
doi: 10.1126/science.abo1984
Lavine, K. et al. Targeting immune–fibroblast crosstalk in myocardial infarction and cardiac fibrosis. Preprint at Research Square https://doi.org/10.21203/rs.3.rs-2402606/v1 (2023). Single-cell and spatial analysis of human and mouse cardiac fibrosis, defining disease-associated macrophages and changes in T cells. Identification of IL-1β
Kuppe, C. et al. Spatial multi-omic map of human myocardial infarction. Nature 608, 766–777 (2022). Multiomic analysis of human post-MI hearts, highlighting myeloid–mesenchymal spatial interactions in cardiac repair.
pubmed: 35948637
pmcid: 9364862
doi: 10.1038/s41586-022-05060-x
Rao, M. et al. Resolving the intertwining of inflammation and fibrosis in human heart failure at single-cell level. Basic Res. Cardiol. 116, 55 (2021).
pubmed: 34601654
doi: 10.1007/s00395-021-00897-1
Dick, S. A. et al. Self-renewing resident cardiac macrophages limit adverse remodeling following myocardial infarction. Nat. Immunol. 20, 29–39 (2019).
pubmed: 30538339
doi: 10.1038/s41590-018-0272-2
Bajpai, G. et al. The human heart contains distinct macrophage subsets with divergent origins and functions. Nat. Med. 24, 1234–1245 (2018).
pubmed: 29892064
pmcid: 6082687
doi: 10.1038/s41591-018-0059-x
Revelo, X. S. et al. Cardiac resident macrophages prevent fibrosis and stimulate angiogenesis. Circ. Res. 129, 1086–1101 (2021).
pubmed: 34645281
pmcid: 8638822
doi: 10.1161/CIRCRESAHA.121.319737
Chaffin, M. et al. Single-nucleus profiling of human dilated and hypertrophic cardiomyopathy. Nature 608, 174–180 (2022).
pubmed: 35732739
doi: 10.1038/s41586-022-04817-8
Alexanian, M. et al. Chromatin remodeling drives immune–fibroblast crosstalk in heart failure pathogenesis. Preprint at bioRxiv https://doi.org/10.1101/2023.01.06.522937 (2023).
Deniset, J. F. et al. Gata6
pubmed: 31315031
pmcid: 7574643
doi: 10.1016/j.immuni.2019.06.010
Litvinukova, M. et al. Cells of the adult human heart. Nature 588, 466–472 (2020).
pubmed: 32971526
pmcid: 7681775
doi: 10.1038/s41586-020-2797-4
Ong, S. et al. Natural killer cells limit cardiac inflammation and fibrosis by halting eosinophil infiltration. Am. J. Pathol. 185, 847–861 (2015).
pubmed: 25622543
pmcid: 4348473
doi: 10.1016/j.ajpath.2014.11.023
Satoh, T. et al. Identification of an atypical monocyte and committed progenitor involved in fibrosis. Nature 541, 96–101 (2017).
pubmed: 28002407
doi: 10.1038/nature20611
Misharin, A. V. et al. Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span. J. Exp. Med. 214, 2387–2404 (2017).
pubmed: 28694385
pmcid: 5551573
doi: 10.1084/jem.20162152
Karlmark, K. R. et al. Hepatic recruitment of the inflammatory Gr1
pubmed: 19554540
doi: 10.1002/hep.22950
Tang, P. M., Nikolic-Paterson, D. J. & Lan, H. Y. Macrophages: versatile players in renal inflammation and fibrosis. Nat. Rev. Nephrol. 15, 144–158 (2019).
pubmed: 30692665
doi: 10.1038/s41581-019-0110-2
Duffield, J. S. et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J. Clin. Invest. 115, 56–65 (2005).
pubmed: 15630444
pmcid: 539199
doi: 10.1172/JCI200522675
Krenkel, O. et al. Therapeutic inhibition of inflammatory monocyte recruitment reduces steatohepatitis and liver fibrosis. Hepatology 67, 1270–1283 (2018).
pubmed: 28940700
doi: 10.1002/hep.29544
Friedman, S. L. et al. A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis. Hepatology 67, 1754–1767 (2018).
pubmed: 28833331
doi: 10.1002/hep.29477
Buechler, M. B., Fu, W. & Turley, S. J. Fibroblast-macrophage reciprocal interactions in health, fibrosis, and cancer. Immunity 54, 903–915 (2021).
pubmed: 33979587
doi: 10.1016/j.immuni.2021.04.021
Ding, L. et al. Bone marrow CD11c
pubmed: 27206766
doi: 10.4049/jimmunol.1502479
Perugorria, M. J. et al. Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage. Gut 68, 533–546 (2019).
pubmed: 29374630
doi: 10.1136/gutjnl-2017-314107
Labiano, I. et al. TREM-2 plays a protective role in cholestasis by acting as a negative regulator of inflammation. J. Hepatol. 77, 991–1004 (2022).
pubmed: 35750136
doi: 10.1016/j.jhep.2022.05.044
Li, Z. et al. Single-cell RNA sequencing depicts the local cell landscape in thyroid-associated ophthalmopathy. Cell Rep. Med 3, 100699 (2022).
pubmed: 35896115
pmcid: 9418739
doi: 10.1016/j.xcrm.2022.100699
Raslan, A. A. et al. Single cell transcriptomics of fibrotic lungs unveils aging-associated alterations in endothelial and epithelial cell regeneration. Preprint at bioRxiv https://doi.org/10.1101/2023.01.17.523179 (2023).
Eyres, M. et al. Spatially resolved deconvolution of the fibrotic niche in lung fibrosis. Cell Rep. 40, 111230 (2022).
pubmed: 35977489
pmcid: 10073410
doi: 10.1016/j.celrep.2022.111230
Chung, B. K., Ogaard, J., Reims, H. M., Karlsen, T. H. & Melum, E. Spatial transcriptomics identifies enriched gene expression and cell types in human liver fibrosis. Hepatol. Commun. 6, 2538–2550 (2022).
pubmed: 35726350
pmcid: 9426406
doi: 10.1002/hep4.2001
Buechler, M. B. et al. Cross-tissue organization of the fibroblast lineage. Nature 593, 575–579 (2021).
pubmed: 33981032
doi: 10.1038/s41586-021-03549-5
Tsukui, T. et al. Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis. Nat. Commun. 11, 1920 (2020).
pubmed: 32317643
pmcid: 7174390
doi: 10.1038/s41467-020-15647-5
Boyd, D. F. et al. Exuberant fibroblast activity compromises lung function via ADAMTS4. Nature 587, 466–471 (2020).
pubmed: 33116313
pmcid: 7883627
doi: 10.1038/s41586-020-2877-5
Filliol, A. et al. Opposing roles of hepatic stellate cell subpopulations in hepatocarcinogenesis. Nature 610, 356–365 (2022).
pubmed: 36198802
pmcid: 9949942
doi: 10.1038/s41586-022-05289-6
Tsukui, T. & Sheppard, D. Tracing the origin of pathologic pulmonary fibroblasts. Preprint at bioRxiv https://doi.org/10.1101/2022.11.18.517147 (2022).
Krishnamurty, A. T. et al. LRRC15
pubmed: 36171287
pmcid: 9630141
doi: 10.1038/s41586-022-05272-1
Nguyen, H. N. et al. Autocrine loop involving IL-6 family member LIF, LIF receptor, and STAT4 drives sustained fibroblast production of inflammatory mediators. Immunity 46, 220–232 (2017).
pubmed: 28228280
pmcid: 5567864
doi: 10.1016/j.immuni.2017.01.004
Ng, B. et al. Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis. Sci. Transl. Med. 11, eaaw1237 (2019).
pubmed: 31554736
doi: 10.1126/scitranslmed.aaw1237
Schafer, S. et al. IL-11 is a crucial determinant of cardiovascular fibrosis. Nature 552, 110–115 (2017).
pubmed: 29160304
pmcid: 5807082
doi: 10.1038/nature24676
Zhou, X. et al. Circuit design features of a stable two-cell system. Cell 172, 744–757 (2018). This study explains the concept of macrophage–fibroblast circuits and how they regulate cell proliferation and steady-state proportions.
pubmed: 29398113
pmcid: 7377352
doi: 10.1016/j.cell.2018.01.015
Adler, M. et al. Principles of cell circuits for tissue repair and fibrosis. iScience 23, 100841 (2020). This study explains the concept of macrophage–fibroblast circuits in fibrosis and the idea of ‘hot’ v ‘cold’ fibrosis.
pubmed: 32058955
pmcid: 7005469
doi: 10.1016/j.isci.2020.100841
Setten, E. et al. Understanding fibrosis pathogenesis via modeling macrophage-fibroblast interplay in immune-metabolic context. Nat. Commun. 13, 6499 (2022).
pubmed: 36310236
pmcid: 9618579
doi: 10.1038/s41467-022-34241-5
Korsunsky, I. et al. Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in four chronic inflammatory diseases. Med 3, 481–518 (2022).
pubmed: 35649411
doi: 10.1016/j.medj.2022.05.002
Wei, K., Nguyen, H. N. & Brenner, M. B. Fibroblast pathology in inflammatory diseases. J. Clin. Invest. 131, e149538 (2021).
pubmed: 34651581
pmcid: 8516469
doi: 10.1172/JCI149538
Lodyga, M. et al. Cadherin-11-mediated adhesion of macrophages to myofibroblasts establishes a profibrotic niche of active TGF-β. Sci. Signal 12, eaao3469 (2019).
pubmed: 30647145
doi: 10.1126/scisignal.aao3469
Umetsu, D. T., Katzen, D., Jabara, H. H. & Geha, R. S. Antigen presentation by human dermal fibroblasts: activation of resting T lymphocytes. J. Immunol. 136, 440–445 (1986).
pubmed: 3484491
doi: 10.4049/jimmunol.136.2.440
Kundig, T. M. et al. Fibroblasts as efficient antigen-presenting cells in lymphoid organs. Science 268, 1343–1347 (1995).
pubmed: 7761853
doi: 10.1126/science.7761853
Elyada, E. et al. Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts. Cancer Discov. 9, 1102–1123 (2019).
pubmed: 31197017
pmcid: 6727976
doi: 10.1158/2159-8290.CD-19-0094
Kerdidani, D. et al. Lung tumor MHCII immunity depends on in situ antigen presentation by fibroblasts. J. Exp. Med. 219, e20210815 (2022).
pubmed: 35029648
pmcid: 8764966
doi: 10.1084/jem.20210815
Ngwenyama, N. et al. Antigen presentation by cardiac fibroblasts promotes cardiac dysfunction. Nat. Cardiovasc. Res. 1, 761–774 (2022).
pubmed: 36092510
pmcid: 9451034
doi: 10.1038/s44161-022-00116-7
Sutherland, T. E., Dyer, D. P. & Allen, J. E. The extracellular matrix and the immune system: a mutually dependent relationship. Science 379, eabp8964 (2023).
pubmed: 36795835
doi: 10.1126/science.abp8964
Malehmir, M. et al. Platelet GPIbα is a mediator and potential interventional target for NASH and subsequent liver cancer. Nat. Med. 25, 641–655 (2019).
pubmed: 30936549
doi: 10.1038/s41591-019-0379-5
Zhuo, L. et al. SHAP potentiates the CD44-mediated leukocyte adhesion to the hyaluronan substratum. J. Biol. Chem. 281, 20303–20314 (2006).
pubmed: 16702221
doi: 10.1074/jbc.M506703200
McQuitty, C. E., Williams, R., Chokshi, S. & Urbani, L. Immunomodulatory role of the extracellular matrix within the liver disease microenvironment. Front. Immunol. 11, 574276 (2020).
pubmed: 33262757
pmcid: 7686550
doi: 10.3389/fimmu.2020.574276
Solis, A. G. et al. Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity. Nature 573, 69–74 (2019).
pubmed: 31435009
pmcid: 6939392
doi: 10.1038/s41586-019-1485-8
Tharp, K. M. et al. Myeloid mechano-metabolic programming restricts anti-tumor immunity. Preprint at bioRxiv https://doi.org/10.1101/2022.07.14.499764 (2022).
Pakshir, P. et al. Dynamic fibroblast contractions attract remote macrophages in fibrillar collagen matrix. Nat. Commun. 10, 1850 (2019).
pubmed: 31015429
pmcid: 6478854
doi: 10.1038/s41467-019-09709-6
Marcellin, P. et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet 381, 468–475 (2013).
pubmed: 23234725
doi: 10.1016/S0140-6736(12)61425-1
Lassailly, G. et al. Bariatric surgery provides long-term resolution of nonalcoholic steatohepatitis and regression of fibrosis. Gastroenterology 159, 1290–1301 (2020).
pubmed: 32553765
doi: 10.1053/j.gastro.2020.06.006
Izawa, H. et al. Mineralocorticoid receptor antagonism ameliorates left ventricular diastolic dysfunction and myocardial fibrosis in mildly symptomatic patients with idiopathic dilated cardiomyopathy: a pilot study. Circulation 112, 2940–2945 (2005).
pubmed: 16275882
doi: 10.1161/CIRCULATIONAHA.105.571653
Diez, J. et al. Losartan-dependent regression of myocardial fibrosis is associated with reduction of left ventricular chamber stiffness in hypertensive patients. Circulation 105, 2512–2517 (2002).
pubmed: 12034658
doi: 10.1161/01.CIR.0000017264.66561.3D
Prabhu, S. et al. Regression of diffuse ventricular fibrosis following restoration of sinus rhythm with catheter ablation in patients with atrial fibrillation and systolic dysfunction: a substudy of the CAMERA MRI Trial. JACC Clin. Electrophysiol. 4, 999–1007 (2018).
pubmed: 30139501
doi: 10.1016/j.jacep.2018.04.013
Fioretto, P., Steffes, M. W., Sutherland, D. E., Goetz, F. C. & Mauer, M. Reversal of lesions of diabetic nephropathy after pancreas transplantation. N. Engl. J. Med. 339, 69–75 (1998).
pubmed: 9654536
doi: 10.1056/NEJM199807093390202
Fioretto, P., Sutherland, D. E., Najafian, B. & Mauer, M. Remodeling of renal interstitial and tubular lesions in pancreas transplant recipients. Kidney Int. 69, 907–912 (2006).
pubmed: 16518350
doi: 10.1038/sj.ki.5000153
Ramachandran, P. et al. Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis. Proc. Natl Acad. Sci. USA 109, E3186–E3195 (2012). This study demonstrates the role of a subpopulation of matrix-degrading monocyte-derived macrophages in liver fibrosis regression.
pubmed: 23100531
pmcid: 3503234
doi: 10.1073/pnas.1119964109
Gibbons, M. A. et al. Ly6C
pubmed: 21680953
doi: 10.1164/rccm.201010-1719OC
Rantakari, P. et al. Stabilin-1 expression defines a subset of macrophages that mediate tissue homeostasis and prevent fibrosis in chronic liver injury. Proc. Natl Acad. Sci. USA 113, 9298–9303 (2016).
pubmed: 27474165
pmcid: 4995933
doi: 10.1073/pnas.1604780113
Takimoto, Y. et al. Myeloid TLR4 signaling promotes post-injury withdrawal resolution of murine liver fibrosis. iScience 26, 106220 (2023).
pubmed: 36876136
pmcid: 9982274
doi: 10.1016/j.isci.2023.106220
Pellicoro, A. et al. Elastin accumulation is regulated at the level of degradation by macrophage metalloelastase (MMP-12) during experimental liver fibrosis. Hepatology 55, 1965–1975 (2012).
pubmed: 22223197
doi: 10.1002/hep.25567
Fallowfield, J. A. et al. Scar-associated macrophages are a major source of hepatic matrix metalloproteinase-13 and facilitate the resolution of murine hepatic fibrosis. J. Immunol. 178, 5288–5295 (2007).
pubmed: 17404313
doi: 10.4049/jimmunol.178.8.5288
Ren, J. et al. Twist1 in infiltrating macrophages attenuates kidney fibrosis via matrix metallopeptidase 13-mediated matrix degradation. J. Am. Soc. Nephrol. 30, 1674–1685 (2019).
pubmed: 31315922
pmcid: 6727252
doi: 10.1681/ASN.2018121253
McKleroy, W., Lee, T. H. & Atabai, K. Always cleave up your mess: targeting collagen degradation to treat tissue fibrosis. Am. J. Physiol. Lung Cell. Mol. Physiol. 304, L709–L721 (2013).
pubmed: 23564511
pmcid: 3680761
doi: 10.1152/ajplung.00418.2012
Cui, H. et al. Monocyte-derived alveolar macrophage apolipoprotein E participates in pulmonary fibrosis resolution. JCI Insight 5, e134539 (2020).
pubmed: 32027623
pmcid: 7141408
doi: 10.1172/jci.insight.134539
Atabai, K. et al. Mfge8 diminishes the severity of tissue fibrosis in mice by binding and targeting collagen for uptake by macrophages. J. Clin. Invest. 119, 3713–3722 (2009).
pubmed: 19884654
pmcid: 2786804
doi: 10.1172/JCI40053
Madsen, D. H. et al. M2-like macrophages are responsible for collagen degradation through a mannose receptor-mediated pathway. J. Cell Biol. 202, 951–966 (2013).
pubmed: 24019537
pmcid: 3776354
doi: 10.1083/jcb.201301081
Campana, L. et al. The STAT3–IL-10–IL-6 pathway is a novel regulator of macrophage efferocytosis and phenotypic conversion in sterile liver injury. J. Immunol. 200, 1169–1187 (2018).
pubmed: 29263216
doi: 10.4049/jimmunol.1701247
Hu, M. et al. Hepatic macrophages act as a central hub for relaxin-mediated alleviation of liver fibrosis. Nat. Nanotechnol. 16, 466–477 (2021).
pubmed: 33495618
doi: 10.1038/s41565-020-00836-6
Saijou, E. et al. Neutrophils alleviate fibrosis in the CCl
pubmed: 29881822
pmcid: 5983199
doi: 10.1002/hep4.1178
Calvente, C. J. et al. Neutrophils contribute to spontaneous resolution of liver inflammation and fibrosis via microRNA-223. J. Clin. Invest. 129, 4091–4109 (2019).
pubmed: 31295147
pmcid: 6763256
doi: 10.1172/JCI122258
Hegde, P. et al. Mucosal-associated invariant T cells are a profibrogenic immune cell population in the liver. Nat. Commun. 9, 2146 (2018).
pubmed: 29858567
pmcid: 5984626
doi: 10.1038/s41467-018-04450-y
Mabire, M. et al. MAIT cell inhibition promotes liver fibrosis regression via macrophage phenotype reprogramming. Nat. Commun. 14, 1830 (2023).
pubmed: 37005415
pmcid: 10067815
doi: 10.1038/s41467-023-37453-5
Baeck, C. et al. Pharmacological inhibition of the chemokine C–C motif chemokine ligand 2 (monocyte chemoattractant protein 1) accelerates liver fibrosis regression by suppressing Ly-6C
pubmed: 24481979
doi: 10.1002/hep.26783
Kisseleva, T. & Brenner, D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat. Rev. Gastroenterol. Hepatol. 18, 151–166 (2021).
pubmed: 33128017
doi: 10.1038/s41575-020-00372-7
Radaeva, S. et al. Natural killer cells ameliorate liver fibrosis by killing activated stellate cells in NKG2D-dependent and tumor necrosis factor-related apoptosis-inducing ligand-dependent manners. Gastroenterology 130, 435–452 (2006).
pubmed: 16472598
doi: 10.1053/j.gastro.2005.10.055
Koda, Y. et al. CD8
pubmed: 34294714
pmcid: 8298513
doi: 10.1038/s41467-021-24734-0
Krizhanovsky, V. et al. Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657–667 (2008).
pubmed: 18724938
pmcid: 3073300
doi: 10.1016/j.cell.2008.06.049
Sagiv, A. et al. Granule exocytosis mediates immune surveillance of senescent cells. Oncogene 32, 1971–1977 (2013).
pubmed: 22751116
doi: 10.1038/onc.2012.206
Troeger, J. S. et al. Deactivation of hepatic stellate cells during liver fibrosis resolution in mice. Gastroenterology 143, 1073–1083 (2012).
pubmed: 22750464
doi: 10.1053/j.gastro.2012.06.036
Kisseleva, T. et al. Myofibroblasts revert to an inactive phenotype during regression of liver fibrosis. Proc. Natl Acad. Sci. USA 109, 9448–9453 (2012).
pubmed: 22566629
pmcid: 3386114
doi: 10.1073/pnas.1201840109
Schwantes-An, T. H. et al. Genome-wide association study and meta-analysis on alcohol-associated liver cirrhosis identifies genetic risk factors. Hepatology 73, 1920–1931 (2021).
pubmed: 32853455
doi: 10.1002/hep.31535
Anstee, Q. M. et al. Genome-wide association study of non-alcoholic fatty liver and steatohepatitis in a histologically characterised cohort
pubmed: 32298765
doi: 10.1016/j.jhep.2020.04.003
Allen, R. J. et al. Genome-wide association study of susceptibility to idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med 201, 564–574 (2020).
pubmed: 31710517
pmcid: 7047454
doi: 10.1164/rccm.201905-1017OC
Nauffal, V. et al. Genetics of myocardial interstitial fibrosis in the human heart and association with disease. Nat. Genet. 55, 777–786 (2023).
pubmed: 37081215
doi: 10.1038/s41588-023-01371-5
Murtha, L. A. et al. The role of pathological aging in cardiac and pulmonary fibrosis. Aging Dis. 10, 419–428 (2019).
pubmed: 31011486
pmcid: 6457057
doi: 10.14336/AD.2018.0601
Kim, I. H., Kisseleva, T. & Brenner, D. A. Aging and liver disease. Curr. Opin. Gastroenterol. 31, 184–191 (2015).
pubmed: 25850346
pmcid: 4736713
doi: 10.1097/MOG.0000000000000176
Lee, S. et al. Molecular programs of fibrotic change in aging human lung. Nat. Commun. 12, 6309 (2021).
pubmed: 34728633
pmcid: 8563941
doi: 10.1038/s41467-021-26603-2
Franceschi, C., Garagnani, P., Parini, P., Giuliani, C. & Santoro, A. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat. Rev. Endocrinol. 14, 576–590 (2018).
pubmed: 30046148
doi: 10.1038/s41574-018-0059-4
Shaw, A. C., Goldstein, D. R. & Montgomery, R. R. Age-dependent dysregulation of innate immunity. Nat. Rev. Immunol. 13, 875–887 (2013).
pubmed: 24157572
pmcid: 4096436
doi: 10.1038/nri3547
Gullotta, G. S. et al. Age-induced alterations of granulopoiesis generate atypical neutrophils that aggravate stroke pathology. Nat. Immunol. 24, 925–940 (2023).
pubmed: 37188941
doi: 10.1038/s41590-023-01505-1
Mogilenko, D. A., Shchukina, I. & Artyomov, M. N. Immune ageing at single-cell resolution. Nat. Rev. Immunol. 22, 484–498 (2022).
pubmed: 34815556
doi: 10.1038/s41577-021-00646-4
De Maeyer, R. P. H. & Chambers, E. S. The impact of ageing on monocytes and macrophages. Immunol. Lett. 230, 1–10 (2021).
pubmed: 33309673
doi: 10.1016/j.imlet.2020.12.003
Govaere, O. et al. A proteo-transcriptomic map of non-alcoholic fatty liver disease signatures. Nat. Metab. 5, 572–578 (2023).
pubmed: 37037945
pmcid: 10132975
doi: 10.1038/s42255-023-00775-1
Abozaid, Y. J. et al. Plasma proteomic signature of fatty liver disease: the Rotterdam Study. Hepatology https://doi.org/10.1097/HEP.0000000000000300 (2023).
Sanyal, A. J. et al. Defining the serum proteomic signature of hepatic steatosis, inflammation, ballooning and fibrosis in non-alcoholic fatty liver disease. J. Hepatol. 78, 693–703 (2023).
pubmed: 36528237
doi: 10.1016/j.jhep.2022.11.029
Bowman, W. S. et al. Proteomic biomarkers of progressive fibrosing interstitial lung disease: a multicentre cohort analysis. Lancet Respir. Med 10, 593–602 (2022).
pubmed: 35063079
pmcid: 9177713
doi: 10.1016/S2213-2600(21)00503-8
McGlinchey, A. J. et al. Metabolic signatures across the full spectrum of non-alcoholic fatty liver disease. JHEP Rep. 4, 100477 (2022).
pubmed: 35434590
pmcid: 9006858
doi: 10.1016/j.jhepr.2022.100477
Seeliger, B. et al. Changes in serum metabolomics in idiopathic pulmonary fibrosis and effect of approved antifibrotic medication. Front Pharm. 13, 837680 (2022).
doi: 10.3389/fphar.2022.837680
Sacchi, M., Bansal, R. & Rouwkema, J. Bioengineered 3D models to recapitulate tissue fibrosis. Trends Biotechnol. 38, 623–636 (2020).
pubmed: 31952833
doi: 10.1016/j.tibtech.2019.12.010