The immunology of rheumatoid arthritis.
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
06
05
2020
accepted:
29
09
2020
pubmed:
2
12
2020
medline:
23
3
2021
entrez:
1
12
2020
Statut:
ppublish
Résumé
The immunopathogenesis of rheumatoid arthritis (RA) spans decades, beginning with the production of autoantibodies against post-translationally modified proteins (checkpoint 1). After years of asymptomatic autoimmunity and progressive immune system remodeling, tissue tolerance erodes and joint inflammation ensues as tissue-invasive effector T cells emerge and protective joint-resident macrophages fail (checkpoint 2). The transition of synovial stromal cells into autoaggressive effector cells converts synovitis from acute to chronic destructive (checkpoint 3). The loss of T cell tolerance derives from defective DNA repair, causing abnormal cell cycle dynamics, telomere fragility and instability of mitochondrial DNA. Mitochondrial and lysosomal anomalies culminate in the generation of short-lived tissue-invasive effector T cells. This differentiation defect builds on a metabolic platform that shunts glucose away from energy generation toward the cell building and motility programs. The next frontier in RA is the development of curative interventions, for example, reprogramming T cell defects during the period of asymptomatic autoimmunity.
Identifiants
pubmed: 33257900
doi: 10.1038/s41590-020-00816-x
pii: 10.1038/s41590-020-00816-x
pmc: PMC8557973
mid: NIHMS1749342
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
10-18Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL142068
Pays : United States
Organisme : BLRD VA
ID : I01 BX001669
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR042527
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL117913
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI108906
Pays : United States
Références
Myasoedova, E., Davis, J., Matteson, E. L. & Crowson, C. S. Is the epidemiology of rheumatoid arthritis changing? Results from a population-based incidence study, 1985–2014. Ann. Rheum. Dis. 79, 440–444 (2020).
pubmed: 32066556
Mahler, M., Martinez-Prat, L., Sparks, J. A. & Deane, K. D. Precision medicine in the care of rheumatoid arthritis: focus on prediction and prevention of future clinically-apparent disease. Autoimmun. Rev. 19, 102506 (2020).
pubmed: 32173516
Eyre, S. et al. High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nat. Genet. 44, 1336–1340 (2012).
pubmed: 23143596
pmcid: 3605761
Alarcón, G. S. Epidemiology of rheumatoid arthritis. Rheum. Dis. Clin. North Am. 21, 589–604 (1995).
pubmed: 8619090
Viatte, S. et al. Association of HLA-DRB1 haplotypes with rheumatoid arthritis severity, mortality, and treatment response. JAMA 313, 1645–1656 (2015).
pubmed: 25919528
pmcid: 4928097
Okada, Y. et al. Risk for ACPA-positive rheumatoid arthritis is driven by shared HLA amino acid polymorphisms in Asian and European populations. Hum. Mol. Genet. 23, 6916–6926 (2014).
pubmed: 25070946
pmcid: 4245039
Amariuta, T., Luo, Y., Knevel, R., Okada, Y. & Raychaudhuri, S. Advances in genetics toward identifying pathogenic cell states of rheumatoid arthritis. Immunol. Rev. 294, 188–204 (2020).
pubmed: 31782165
Hu, X. et al. Regulation of gene expression in autoimmune disease loci and the genetic basis of proliferation in CD4
pubmed: 24968232
pmcid: 4072514
Goronzy, J. J. & Weyand, C. M. Mechanisms underlying T cell ageing. Nat. Rev. Immunol. 19, 573–583 (2019).
pubmed: 31186548
pmcid: 7584388
Goronzy, J. J. & Weyand, C. M. Successful and maladaptive T cell aging. Immunity 46, 364–378 (2017).
pubmed: 28329703
pmcid: 5433436
Arbuckle, M. R. et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N. Engl. J. Med. 349, 1526–1533 (2003).
pubmed: 14561795
McClain, M. T. et al. The prevalence, onset, and clinical significance of antiphospholipid antibodies prior to diagnosis of systemic lupus erythematosus. Arthritis Rheum. 50, 1226–1232 (2004).
pubmed: 15077305
Aho, K., Heliövaara, M., Maatela, J., Tuomi, T. & Palosuo, T. Rheumatoid factors antedating clinical rheumatoid arthritis. J. Rheumatol. 18, 1282–1284 (1991).
pubmed: 1757925
Deane, K. D., Norris, J. M. & Holers, V. M. Preclinical rheumatoid arthritis: identification, evaluation, and future directions for investigation. Rheum. Dis. Clin. North Am. 36, 213–241 (2010).
pubmed: 20510231
pmcid: 2879710
van Delft, M. A. M. & Huizinga, T. W. J. An overview of autoantibodies in rheumatoid arthritis. J. Autoimmun. 110, 102392 (2020).
pubmed: 31911013
Ligier, S., Fortin, P. R. & Newkirk, M. M. A new antibody in rheumatoid arthritis targeting glycated IgG: IgM anti-IgG-AGE. Br. J. Rheumatol. 37, 1307–1314 (1998).
pubmed: 9973155
Raposo, B. et al. T cells specific for post-translational modifications escape intrathymic tolerance induction. Nat. Commun. 9, 353 (2018).
pubmed: 29367624
pmcid: 5783942
Berglin, E. et al. A combination of autoantibodies to cyclic citrullinated peptide (CCP) and HLA-DRB1 locus antigens is strongly associated with future onset of rheumatoid arthritis. Arthritis Res. Ther. 6, R303–R308 (2004).
pubmed: 15225365
pmcid: 464874
Johansson, M., Arlestig, L., Hallmans, G. & Rantapää-Dahlqvist, S. PTPN22 polymorphism and anti-cyclic citrullinated peptide antibodies in combination strongly predicts future onset of rheumatoid arthritis and has a specificity of 100% for the disease. Arthritis Res. Ther. 8, R19 (2006).
pubmed: 16507117
Ge, C. & Holmdahl, R. The structure, specificity and function of anti-citrullinated protein antibodies. Nat. Rev. Rheumatol. 15, 503–508 (2019).
pubmed: 31253945
Kissel, T. et al. Antibodies and B cells recognising citrullinated proteins display a broad cross-reactivity towards other post-translational modifications. Ann. Rheum. Dis. 79, 472–480 (2020).
pubmed: 32041746
Makrygiannakis, D. et al. Smoking increases peptidylarginine deiminase 2 enzyme expression in human lungs and increases citrullination in BAL cells. Ann. Rheum. Dis. 67, 1488–1492 (2008).
pubmed: 18413445
Holers, V. M. et al. Rheumatoid arthritis and the mucosal origins hypothesis: protection turns to destruction. Nat. Rev. Rheumatol. 14, 542–557 (2018).
pubmed: 30111803
pmcid: 6704378
Khandpur, R. et al. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. Sci. Transl. Med. 5, 178ra140 (2013).
Carmona-Rivera, C. et al. Synovial fibroblast-neutrophil interactions promote pathogenic adaptive immunity in rheumatoid arthritis. Sci. Immunol. 2, eaag3358 (2017).
pubmed: 28649674
pmcid: 5479641
Schönland, S. O. et al. Premature telomeric loss in rheumatoid arthritis is genetically determined and involves both myeloid and lymphoid cell lineages. Proc. Natl Acad. Sci. USA 100, 13471–13476 (2003).
pubmed: 14578453
Waase, I., Kayser, C., Carlson, P. J., Goronzy, J. J. & Weyand, C. M. Oligoclonal T cell proliferation in patients with rheumatoid arthritis and their unaffected siblings. Arthritis Rheum. 39, 904–913 (1996).
pubmed: 8651983
Gerlag, D. M. et al. Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: the PRAIRI study. Ann. Rheum. Dis. 78, 179–185 (2019).
pubmed: 30504445
Kissel, T. et al. On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis. Ann. Rheum. Dis. 78, 1616–1620 (2019).
pubmed: 31471298
Scher, J. U. et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife 2, e01202 (2013).
pubmed: 24192039
pmcid: 3816614
Humby, F. et al. Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients. Ann. Rheum. Dis. 78, 761–772 (2019).
pubmed: 30878974
pmcid: 6579551
Lewis, M. J. et al. Molecular portraits of early rheumatoid arthritis identify clinical and treatment response phenotypes. Cell Rep. 28, 2455–2470.e5 (2019).
pubmed: 31461658
pmcid: 6718830
Ponchel, F. et al. T-cell subset abnormalities predict progression along the Inflammatory Arthritis disease continuum: implications for management. Sci. Rep. 10, 3669 (2020).
pubmed: 32111870
pmcid: 7048829
Bader, L. et al. Candidate markers for stratification and classification in rheumatoid arthritis. Front. Immunol. 10, 1488 (2019).
pubmed: 31338093
pmcid: 6626904
Pitaksalee, R. et al. Differential CpG DNA methylation in peripheral naive CD4
pubmed: 32264938
pmcid: 7137446
Tuncel, J. et al. Self-reactive T cells induce and perpetuate chronic relapsing arthritis. Arthritis Res. Ther. 22, 95 (2020).
pubmed: 32345366
pmcid: 7187533
Weyand, C. M. & Goronzy, J. J. Immunometabolism in early and late stages of rheumatoid arthritis. Nat. Rev. Rheumatol. 13, 291–301 (2017).
pubmed: 28360422
pmcid: 6820517
Weyand, C. M., Shen, Y. & Goronzy, J. J. Redox-sensitive signaling in inflammatory T cells and in autoimmune disease. Free Radic. Biol. Med. 125, 36–43 (2018).
pubmed: 29524605
pmcid: 6128787
Wu, B., Goronzy, J. J. & Weyand, C. M. Metabolic fitness of T cells in autoimmune disease. Immunometabolism 2, e200017 (2020).
pubmed: 32477606
pmcid: 7261019
Li, Y., Goronzy, J. J. & Weyand, C. M. DNA damage, metabolism and aging in pro-inflammatory T cells: rheumatoid arthritis as a model system. Exp. Gerontol. 105, 118–127 (2018).
pubmed: 29101015
Wagner, U. G., Koetz, K., Weyand, C. M. & Goronzy, J. J. Perturbation of the T cell repertoire in rheumatoid arthritis. Proc. Natl Acad. Sci. USA 95, 14447–14452 (1998).
pubmed: 9826720
Koetz, K. et al. T cell homeostasis in patients with rheumatoid arthritis. Proc. Natl Acad. Sci. USA 97, 9203–9208 (2000).
pubmed: 10922071
Burgoyne, C. H. et al. Abnormal T cell differentiation persists in patients with rheumatoid arthritis in clinical remission and predicts relapse. Ann. Rheum. Dis. 67, 750–757 (2008).
pubmed: 17644540
Ponchel, F. et al. Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis. Blood 100, 4550–4556 (2002).
pubmed: 12393721
Weyand, C. M., Fujii, H., Shao, L. & Goronzy, J. J. Rejuvenating the immune system in rheumatoid arthritis. Nat. Rev. Rheumatol. 5, 583–588 (2009).
pubmed: 19798035
Weyand, C. M., Shao, L. & Goronzy, J. J. Immune aging and rheumatoid arthritis. Rheum. Dis. Clin. North Am. 36, 297–310 (2010).
pubmed: 20510235
pmcid: 2914095
Weyand, C. M., Yang, Z. & Goronzy, J. J. T cell aging in rheumatoid arthritis. Curr. Opin. Rheumatol. 26, 93–100 (2014).
pubmed: 24296720
pmcid: 3984035
Goronzy, J. J., Li, G., Yang, Z. & Weyand, C. M. The Janus head of T cell aging—autoimmunity and immunodeficiency. Front. Immunol. 4, 131 (2013).
pubmed: 23761790
pmcid: 3671290
Li, Y. et al. Deficient activity of the nuclease MRE11A induces T cell aging and promotes arthritogenic effector functions in patients with rheumatoid arthritis. Immunity 45, 903–916 (2016).
pubmed: 27742546
pmcid: 5123765
Shao, L. et al. Deficiency of the DNA repair enzyme ATM in rheumatoid arthritis. J. Exp. Med. 206, 1435–1449 (2009).
pubmed: 19451263
pmcid: 2715066
Burger, K., Ketley, R. F. & Gullerova, M. Beyond the trinity of ATM, ATR, and DNA-PK: multiple kinases shape the DNA damage response in concert with RNA metabolism. Front. Mol. Biosci. 6, 61 (2019).
pubmed: 31428617
pmcid: 6688092
Yang, Z. et al. Restoring oxidant signaling suppresses proarthritogenic T cell effector functions in rheumatoid arthritis. Sci. Transl. Med. 8, 331ra338 (2016).
Amsen, D., Backer, R. A. & Helbig, C. Decisions on the road to memory. Adv. Exp. Med. Biol. 785, 107–120 (2013).
pubmed: 23456843
Shao, L., Goronzy, J. J. & Weyand, C. M. DNA-dependent protein kinase catalytic subunit mediates T-cell loss in rheumatoid arthritis. EMBO Mol. Med. 2, 415–427 (2010).
pubmed: 20878914
pmcid: 3017722
Li, Y. et al. The DNA repair nuclease MRE11A functions as a mitochondrial protector and prevents T cell pyroptosis and tissue inflammation. Cell Metab. 30, 477–492 e6 (2019).
pubmed: 31327667
pmcid: 7093039
Syed, A. & Tainer, J. A. The MRE11–RAD50–NBS1 complex conducts the orchestration of damage signaling and outcomes to stress in DNA replication and repair. Annu. Rev. Biochem. 87, 263–294 (2018).
pubmed: 29709199
pmcid: 6076887
Mathur, A., Hayward, J. A. & Man, S. M. Molecular mechanisms of inflammasome signaling. J. Leukoc. Biol. 103, 233–257 (2018).
pubmed: 28855232
Mehta, P. & Manson, J. J. What is the clinical relevance of TNF inhibitor immunogenicity in the management of patients with rheumatoid arthritis? Front. Immunol. 11, 589 (2020).
pubmed: 32318070
pmcid: 7154129
Balsa, A. et al. Drug immunogenicity in patients with inflammatory arthritis and secondary failure to tumour necrosis factor inhibitor therapies: the REASON study. Rheumatology (Oxford) 57, 688–693 (2018).
Ponchel, F. et al. Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphopenia. Arthritis Res. Ther. 7, R80–R92 (2005).
pubmed: 15642146
Schmidt, D., Goronzy, J. J. & Weyand, C. M. CD4
pubmed: 8621791
pmcid: 507276
Weyand, C. M., Brandes, J. C., Schmidt, D., Fulbright, J. W. & Goronzy, J. J. Functional properties of CD4
pubmed: 9720647
Yamada, H. et al. Interleukin-15 selectively expands CD57
pubmed: 17644042
Weyand, C. M., Fulbright, J. W. & Goronzy, J. J. Immunosenescence, autoimmunity, and rheumatoid arthritis. Exp. Gerontol. 38, 833–841 (2003).
pubmed: 12915205
Liuzzo, G. et al. Perturbation of the T-cell repertoire in patients with unstable angina. Circulation 100, 2135–2139 (1999).
pubmed: 10571971
Liuzzo, G. et al. Monoclonal T-cell proliferation and plaque instability in acute coronary syndromes. Circulation 101, 2883–2888 (2000).
pubmed: 10869258
Gerli, R. et al. CD4
pubmed: 15159291
Ormseth, M. J. et al. Telomere length and coronary atherosclerosis in rheumatoid arthritis. J. Rheumatol. 43, 1469–1474 (2016).
pubmed: 27252422
pmcid: 4970932
Liuzzo, G. et al. Molecular fingerprint of interferon-γ signaling in unstable angina. Circulation 103, 1509–1514 (2001).
pubmed: 11257077
Fasth, A. E. R., Björkström, N. K., Anthoni, M., Malmberg, K.-J. & Malmström, V. Activating NK-cell receptors co-stimulate CD4
pubmed: 19904767
Warrington, K. J., Takemura, S., Goronzy, J. J. & Weyand, C. M. CD4+,CD28– T cells in rheumatoid arthritis patients combine features of the innate and adaptive immune systems. Arthritis Rheum. 44, 13–20 (2001).
pubmed: 11212151
Snyder, M. R., Nakajima, T., Leibson, P. J., Weyand, C. M. & Goronzy, J. J. Stimulatory killer Ig-like receptors modulate T cell activation through DAP12-dependent and DAP12-independent mechanisms. J. Immunol. 173, 3725–3731 (2004).
pubmed: 15356118
Snyder, M. R., Lucas, M., Vivier, E., Weyand, C. M. & Goronzy, J. J. Selective activation of the c-Jun NH
pubmed: 12591902
pmcid: 2193867
Pereira, B. I. et al. Sestrins induce natural killer function in senescent-like CD8
pubmed: 32231301
Zhang, F. et al. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat. Immunol. 20, 928–942 (2019).
pubmed: 31061532
pmcid: 6602051
Fonseka, C. Y. et al. Mixed-effects association of single cells identifies an expanded effector CD4
pubmed: 30333237
pmcid: 6448773
Colmegna, I. et al. Defective proliferative capacity and accelerated telomeric loss of hematopoietic progenitor cells in rheumatoid arthritis. Arthritis Rheum. 58, 990–1000 (2008).
pubmed: 18383391
pmcid: 2820283
Makowski, L., Chaib, M. & Rathmell, J. C. Immunometabolism: from basic mechanisms to translation. Immunol. Rev. 295, 5–14 (2020).
pubmed: 32320073
Shen, Y. et al. Metabolic control of the scaffold protein TKS5 in tissue-invasive, proinflammatory T cells. Nat. Immunol. 18, 1025–1034 (2017).
pubmed: 28737753
pmcid: 5568495
Yang, Z., Fujii, H., Mohan, S. V., Goronzy, J. J. & Weyand, C. M. Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox balance in rheumatoid arthritis T cells. J. Exp. Med. 210, 2119–2134 (2013).
pubmed: 24043759
pmcid: 3782046
Yang, Z., Goronzy, J. J. & Weyand, C. M. The glycolytic enzyme PFKFB3/phosphofructokinase regulates autophagy. Autophagy 10, 382–383 (2014).
pubmed: 24351650
Yang, Z., Matteson, E. L., Goronzy, J. J. & Weyand, C. M. T-cell metabolism in autoimmune disease. Arthritis Res. Ther. 17, 29 (2015).
pubmed: 25890351
pmcid: 4324046
Weyand, C. M., Wu, B. & Goronzy, J. J. The metabolic signature of T cells in rheumatoid arthritis. Curr. Opin. Rheumatol. 32, 159–167 (2020).
pubmed: 31895885
Ling, G. S. et al. C1q restrains autoimmunity and viral infection by regulating CD8
pubmed: 29724957
pmcid: 6545171
Wen, Z. et al. N-myristoyltransferase deficiency impairs activation of kinase AMPK and promotes synovial tissue inflammation. Nat. Immunol. 20, 313–325 (2019).
pubmed: 30718913
pmcid: 6396296
Krishnan, S. et al. Alterations in lipid raft composition and dynamics contribute to abnormal T cell responses in systemic lupus erythematosus. J. Immunol. 172, 7821–7831 (2004).
pubmed: 15187166
Fernandez, D. & Perl, A. Metabolic control of T cell activation and death in SLE. Autoimmun. Rev. 8, 184–189 (2009).
pubmed: 18722557
Fernandez, D. R. et al. Activation of mammalian target of rapamycin controls the loss of TCRζ in lupus T cells through HRES-1/Rab4-regulated lysosomal degradation. J. Immunol. 182, 2063–2073 (2009).
pubmed: 19201859
pmcid: 2676112
Choi, S.-C. et al. Inhibition of glucose metabolism selectively targets autoreactive follicular helper T cells. Nat. Commun. 9, 4369 (2018).
pubmed: 30348969
pmcid: 6197193
Kono, M. et al. Pyruvate dehydrogenase phosphatase catalytic subunit 2 limits Th17 differentiation. Proc. Natl Acad. Sci. USA 115, 9288–9293 (2018).
pubmed: 30150402
Kono, M. et al. Pyruvate kinase M2 is requisite for Th1 and Th17 differentiation. JCI Insight 4, e127395 (2019).
pmcid: 6629104
Taylor, P. C. & Law, S. T. When the first visit to the rheumatologist is established rheumatoid arthritis. Best Pract. Res. Clin. Rheumatol. 33, 101479 (2020).
Verburg, R. J. et al. Outcome of intensive immunosuppression and autologous stem cell transplantation in patients with severe rheumatoid arthritis is associated with the composition of synovial T cell infiltration. Ann. Rheum. Dis. 64, 1397–1405 (2005).
pubmed: 15829573
pmcid: 1755245
Law, S. T. & Taylor, P. C. Role of biological agents in treatment of rheumatoid arthritis. Pharmacol. Res. 150, 104497 (2019).
pubmed: 31629903
Nygaard, G. & Firestein, G. S. Restoring synovial homeostasis in rheumatoid arthritis by targeting fibroblast-like synoviocytes. Nat. Rev. Rheumatol. 16, 316–333 (2020).
pubmed: 32393826
Takemura, S. et al. Lymphoid neogenesis in rheumatoid synovitis. J. Immunol. 167, 1072–1080 (2001).
pubmed: 11441118
Grumbach, I. M. & Nguyen, E. K. Metabolic stress: mitochondrial function in neointimal formation. Arterioscler. Thromb. Vasc. Biol. 39, 991–997 (2019).
pubmed: 31070466
pmcid: 6531338
Wadey, K., Lopes, J., Bendeck, M. & George, S. Role of smooth muscle cells in coronary artery bypass grafting failure. Cardiovasc. Res. 114, 601–610 (2018).
pubmed: 29373656
pmcid: 5852543
Tinajero, M. G. & Gotlieb, A. I. Recent developments in vascular adventitial pathobiology: the dynamic adventitia as a complex regulator of vascular disease. Am. J. Pathol. 190, 520–534 (2020).
pubmed: 31866347
Croft, A. P. et al. Rheumatoid synovial fibroblasts differentiate into distinct subsets in the presence of cytokines and cartilage. Arthritis Res. Ther. 18, 270 (2016).
pubmed: 27863512
pmcid: 5116193
Mizoguchi, F. et al. Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis. Nat. Commun. 9, 789 (2018).
pubmed: 29476097
pmcid: 5824882
Croft, A. P. et al. Distinct fibroblast subsets drive inflammation and damage in arthritis. Nature 570, 246–251 (2019).
pubmed: 31142839
pmcid: 6690841
Finch, R. et al. Results of a phase 2 study of RG6125, an anti-cadherin-11 monoclonal antibody, in rheumatoid arthritis patients with an inadequate response to anti-TNFalpha therapy. Ann. Rheum. Dis. 78, abstr. OP0224 (2019).
Orr, C. et al. Synovial tissue research: a state-of-the-art review. Nat. Rev. Rheumatol. 13, 463–475 (2017).
pubmed: 28701760
Davies, L. C., Jenkins, S. J., Allen, J. E. & Taylor, P. R. Tissue-resident macrophages. Nat. Immunol. 14, 986–995 (2013).
pubmed: 24048120
pmcid: 4045180
Chakarov, S. et al. Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches. Science 363, eaau0964 (2019).
pubmed: 30872492
Molawi, K. & Sieweke, M. H. Monocytes compensate Kupffer cell loss during bacterial infection. Immunity 42, 10–12 (2015).
pubmed: 25607453
Murray, P. J. Immune regulation by monocytes. Semin. Immunol. 35, 12–18 (2018).
pubmed: 29290545
Murray, P. J. Macrophage polarization. Annu. Rev. Physiol. 79, 541–566 (2017).
pubmed: 27813830
Udalova, I. A., Mantovani, A. & Feldmann, M. Macrophage heterogeneity in the context of rheumatoid arthritis. Nat. Rev. Rheumatol. 12, 472–485 (2016).
pubmed: 27383913
Herenius, M. M. et al. Monocyte migration to the synovium in rheumatoid arthritis patients treated with adalimumab. Ann. Rheum. Dis. 70, 1160–1162 (2011).
pubmed: 21345816
pmcid: 3086080
Culemann, S. et al. Locally renewing resident synovial macrophages provide a protective barrier for the joint. Nature 572, 670–675 (2019).
pubmed: 31391580
pmcid: 6805223
Kuo, D. et al. HBEGF
pubmed: 31068444
pmcid: 6726376
Kang, Y. M. et al. CD8 T cells are required for the formation of ectopic germinal centers in rheumatoid synovitis. J. Exp. Med. 195, 1325–1336 (2002).
pubmed: 12021312
pmcid: 2193749
Crotty, S. Follicular helper CD4 T cells (T
pubmed: 21314428
Bocharnikov, A. V. et al. PD-1
pmcid: 6824311
Rao, D. A. et al. Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis. Nature 542, 110–114 (2017).
pubmed: 28150777
pmcid: 5349321
Wang, S. et al. IL-21 drives expansion and plasma cell differentiation of autoreactive CD11c
pubmed: 29717110
pmcid: 5931508
Wu, B. et al. Succinyl-CoA ligase deficiency in pro-inflammatory and tissue-invasive T cells. Cell Metab. (in the press).