Neuromedin U promotes human type 2 immune responses.
Journal
Mucosal immunology
ISSN: 1935-3456
Titre abrégé: Mucosal Immunol
Pays: United States
ID NLM: 101299742
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
05
01
2022
accepted:
21
06
2022
revised:
25
05
2022
pubmed:
10
7
2022
medline:
20
8
2022
entrez:
9
7
2022
Statut:
ppublish
Résumé
Type 2 immunity mediates the immune responses against parasites and allergic stimuli. Evidence from studies of cell lines and animals implies that neuromedin U (NmU) acts as a pro-inflammatory mediator of type 2 inflammation. However, the role of NmU in human type 2 immunity remains unclear. Here we investigated the expression of NmU in human blood and airways, and the expression of NmU receptors by human immune cells in blood and lung tissue. We detected human NmU (hNmU-25) in blood and airways with higher concentrations in the latter. NmU receptor 1 (NmUR1) was expressed by most human immune cells with higher levels in type 2 cells including type 2 T helpers, type 2 cytotoxic T cells, group-2 innate lymphoid cells and eosinophils, and was upregulated in lung-resident and activated type 2 cells. We also assessed the effects of NmU in these cells. hNmU-25 elicited type 2 cytokine production by type 2 lymphocytes and induced cell migration, including eosinophils. hNmU-25 also enhanced the type 2 immune response to other stimuli, particularly prostaglandin D
Identifiants
pubmed: 35810259
doi: 10.1038/s41385-022-00543-6
pii: S1933-0219(22)00017-4
pmc: PMC9385483
doi:
Substances chimiques
Neuropeptides
0
Peptide Hormones
0
neuromedin U
117505-80-3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
990-999Subventions
Organisme : Department of Health
Pays : United Kingdom
Organisme : Medical Research Council
ID : 1946480
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT222426/Z/21/Z
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
Références
Pulendran, B. & Artis, D. New paradigms in type 2 immunity. Science 337, 431–435 (2012).
pubmed: 22837519
pmcid: 4078898
doi: 10.1126/science.1221064
Green, R. H. et al. Asthma exacerbations and sputum eosinophil counts: A randomised controlled trial. Lancet 360, 1715–1721 (2002).
pubmed: 12480423
doi: 10.1016/S0140-6736(02)11679-5
Siva, R. et al. Eosinophilic airway inflammation and exacerbations of COPD: A randomised controlled trial. Eur. Respir. J. 29, 906–913 (2007).
pubmed: 17301099
doi: 10.1183/09031936.00146306
Jacobsen, E. A. et al. Eosinophil knockout humans: Uncovering the role of eosinophils through eosinophil-directed biological therapies. Annu. Rev. Immunol. 39, 719–757 (2021).
pubmed: 33646859
pmcid: 8317994
doi: 10.1146/annurev-immunol-093019-125918
Mjösberg, J. M. et al. Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. Nat. Immunol. 12, 1055–1062 (2011).
pubmed: 21909091
doi: 10.1038/ni.2104
Caminati, M. et al. Type 2 immunity in asthma. World Allergy Organ. J. 11, 13 (2018).
pubmed: 29988331
pmcid: 6020328
doi: 10.1186/s40413-018-0192-5
Hilvering, B. et al. Synergistic activation of pro-inflammatory type-2 CD8
pubmed: 29907870
pmcid: 6448764
doi: 10.1038/s41385-018-0049-9
Kabata, H. & Artis, D. Neuro-immune crosstalk and allergic inflammation. J. Clin. Invest. 129, 1475–1482 (2019).
pubmed: 30829650
pmcid: 6436850
doi: 10.1172/JCI124609
Ding, W. et al. Calcitonin gene-related peptide biases Langerhans cells toward Th2-type immunity. J. Immunol. 181, 6020–6026 (2008).
pubmed: 18941191
doi: 10.4049/jimmunol.181.9.6020
Nussbaum, J. C. et al. Type 2 innate lymphoid cells control eosinophil homeostasis. Nature 502, 245–248 (2013).
pubmed: 24037376
pmcid: 3795960
doi: 10.1038/nature12526
Sui, P. et al. Pulmonary neuroendocrine cells amplify allergic asthma responses. Science 360, eaan8546 (2018).
pubmed: 29599193
pmcid: 6387886
doi: 10.1126/science.aan8546
Johnson, E. N. et al. Neuromedin elicits cytokine release in murine Th2-type T cell clone D10.G4.1. J. Immunol. 173, 7230–7238 (2004).
pubmed: 15585845
doi: 10.4049/jimmunol.173.12.7230
Cardoso, V. et al. Neuronal regulation of type 2 innate lymphoid cells via neuromedin U. Nature 549, 277–281 (2017).
pubmed: 28869974
pmcid: 5714273
doi: 10.1038/nature23469
Klose, C. S. N. et al. The neuropeptide neuromedin U stimulates innate lymphoid cells and type 2 inflammation. Nature 549, 282–286 (2017).
pubmed: 28869965
pmcid: 6066372
doi: 10.1038/nature23676
Wallrapp, A. et al. The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation. Nature 549, 351–356 (2017).
pubmed: 28902842
pmcid: 5746044
doi: 10.1038/nature24029
Minamino, N. et al. Neuromedin U-8 and U-25: Novel uterus stimulating and hypertensive peptides identified in porcine spinal cord. Biochem. Biophys. Res. Commun. 130, 1078–1085 (1985).
pubmed: 3839674
doi: 10.1016/0006-291X(85)91726-7
Austin, C. et al. Cloning and characterization of the cDNA encoding the human neuromedin U (NmU) precursor: NmU expression in the human gastrointestinal tract. J. Mol. Endocrinol. 14, 157–169 (1995).
pubmed: 7619205
doi: 10.1677/jme.0.0140157
Raddatz, R. et al. Identification and characterization of two neuromedin U receptors differentially expressed in peripheral tissues and the central nervous system. J. Biol. Chem. 275, 32452–32459 (2000).
pubmed: 10899166
doi: 10.1074/jbc.M004613200
Martinez, V. G. & O’Driscoll, L. Neuromedin U: A multifunctional neuropeptide with pleiotropic roles. Clin. Chem. 61, 471–482 (2015).
pubmed: 25605682
doi: 10.1373/clinchem.2014.231753
Moriyama, M. et al. The neuropeptide neuromedin U activates eosinophils and is involved in allergen-induced eosinophilia. Am. J. Physiol. Lung. Cell. Mol. Physiol. 290, L971–L977 (2006).
pubmed: 16373672
doi: 10.1152/ajplung.00345.2005
Ye, Y. et al. Neuromedin U: Potential roles in immunity and inflammation. Immunology 162, 17–29 (2021).
pubmed: 32888314
doi: 10.1111/imm.13257
Spits, H. & Mjösberg, J. M. Heterogeneity of type 2 innate lymphoid cells. Nat. Rev. Immunol. 30, 1–12 (2022).
Shafiei-Jahani, P. et al. CD200-CD200R immune checkpoint engagement regulates ILC2 effector function and ameliorates lung inflammation in asthma. Nat. Commun. 12, 2526 (2021).
pubmed: 33953190
pmcid: 8100131
doi: 10.1038/s41467-021-22832-7
Xue, L. et al. Prostaglandin D
pubmed: 24388011
pmcid: 3979107
doi: 10.1016/j.jaci.2013.10.056
Xue, L. et al. Prostaglandin D
pubmed: 16272307
doi: 10.4049/jimmunol.175.10.6531
Salimi, M. et al. Cysteinyl leukotriene E
pubmed: 28115217
pmcid: 5624780
doi: 10.1016/j.jaci.2016.12.958
Kay, A. B. et al. A role for eosinophils in airway remodelling in asthma. Trends Immunol. 25, 477–482 (2004).
pubmed: 15324740
doi: 10.1016/j.it.2004.07.006
Choi, E. N. et al. A parallel signal-transduction pathway for eotaxin- and interleukin-5-induced eosinophil shape change. Immunology 108, 245–256 (2003).
pubmed: 12562334
pmcid: 1782875
doi: 10.1046/j.1365-2567.2003.01565.x
Moriyama, M. et al. The neuropeptide neuromedin U promotes IL-6 production from macrophages and endotoxin shock. Biochem. Biophy. Res. Commun. 341, 1149–1154 (2006).
doi: 10.1016/j.bbrc.2006.01.075
Moriyama, M. et al. The neuropeptide neuromedin U promotes inflammation by direct activation of mast cells. J. Exp. Med. 202, 217–224 (2005).
pubmed: 16009716
pmcid: 2213011
doi: 10.1084/jem.20050248
Mitchell, J. D. et al. Expression and vasoconstrictor function of anorexigenic peptides neuromedin U-25 and S in the human cardiovascular system. Cardiovasc. Res. 81, 353–361 (2009).
pubmed: 18987052
doi: 10.1093/cvr/cvn302
Szekeres, P. G. et al. Neuromedin U is a potent agonist at the orphan G protein-coupled receptor FM3. J. Biol. Chem. 275, 20247–20250 (2000).
pubmed: 10811630
doi: 10.1074/jbc.C000244200
Howard, A. D. et al. Identification of receptors for neuromedin U and its role in feeding. Nature 406, 70–74 (2000).
pubmed: 10894543
doi: 10.1038/35017610
Griesenauer, B. & Paczesny, S. The ST2/IL-33 axis in immune cells during inflammatory diseases. Front. Immunol. 8, 475 (2017).
pubmed: 28484466
pmcid: 5402045
doi: 10.3389/fimmu.2017.00475
Xue, L. et al. Prostaglandin D
pubmed: 25441644
pmcid: 4418751
doi: 10.1016/j.jaci.2014.09.006
Cheng, D. et al. Epithelial interleukin-25 is a key mediator in Th2-high, corticosteroid-responsive asthma. Am. J. Respir. Crit. Care. Med. 190, 639–648 (2014).
pubmed: 25133876
pmcid: 4214109
doi: 10.1164/rccm.201403-0505OC
Préfontaine, D. et al. Increased IL-33 expression by epithelial cells in bronchial asthma. J. Allergy Clin. Immunol. 125, 752–754 (2010).
pubmed: 20153038
doi: 10.1016/j.jaci.2009.12.935
Ying, S. et al. Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity. J. Immunol. 174, 8183–8190 (2005).
pubmed: 15944327
doi: 10.4049/jimmunol.174.12.8183
Fajt, M. L. et al. Prostaglandin D
pubmed: 23506843
pmcid: 3889167
doi: 10.1016/j.jaci.2013.01.035
Xue, L. et al. Novel function of CRTH2 in prevent- ing apoptosis of human Th2 cells through activation of the phosphatidylinositol 3-kinase pathway. J. Immunol. 182, 7580–7586 (2009).
pubmed: 19494281
doi: 10.4049/jimmunol.0804090
Corren, J. et al. Tezepelumab in adults with uncontrolled asthma. N. Engl. J. Med. 377, 936–946 (2017).
pubmed: 28877011
doi: 10.1056/NEJMoa1704064
Singh, D. et al. CRTH2 antagonists in asthma: Current perspectives. Clin. Pharmacol. 9, 165–173 (2017).
pubmed: 29276415
pmcid: 5733922
Asano, K. et al. A phase 2a study of DP2 antagonist GB001 for asthma. J. Allergy Clin. Immunol. Pr. 8, 1275–1283.e1 (2020).
doi: 10.1016/j.jaip.2019.11.016
Kaul, M. et al. First-in-human study demonstrating the safety and clinical efficacy of novel anti-IL-17A monoclonal antibody CJM112 in moderate to severe plaque psoriasis. J. Eur. Acad. Dermatol. Venereol. 35, 1143–1151 (2021).
pubmed: 33617042
pmcid: 8246720
doi: 10.1111/jdv.17071
Hosoya, M. et al. Identification and functional characterization of a novel subtype of neuromedin U receptor. J. Biol. Chem. 275, 29528–29532 (2000).
pubmed: 10887190
doi: 10.1074/jbc.M004261200
Nagata, K. & Hirai, H. The second PGD
doi: 10.1016/S0952-3278(03)00078-4
Brighton, P. J. et al. Signaling and ligand binding by recombinant neuromedin U receptors/evidence for dual coupling to Gaq/11 and Gai and an irreversible ligand-receptor interaction. Mol. Pharmacol. 66, 1544–1556 (2004).
pubmed: 15331768
doi: 10.1124/mol.104.002337
Xue, L. et al. Inhibition of PI3K and calcineurin suppresses chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2)-dependent responses of Th2 lymphocytes to prostaglandin D
pubmed: 17196174
doi: 10.1016/j.bcp.2006.11.021
Stone, K. D. et al. IgE, mast cells, basophils, and eosinophils. J. Allergy Clin. Immunol. 125, S73–S80 (2010).
pubmed: 20176269
pmcid: 2847274
doi: 10.1016/j.jaci.2009.11.017
Nair, P. What is an “eosinophilic phenotype” of asthma? J. Allergy Clin. Immunol. 132, 81–83 (2013).
pubmed: 23727039
doi: 10.1016/j.jaci.2013.05.007
Chung, K. F. et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur. Respir. J. 43, 343–373 (2014).
pubmed: 24337046
doi: 10.1183/09031936.00202013