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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2019

Open Access 01-12-2019 | Endometriosis | Research

CD4+/CD8+ mucosa-associated invariant T cells foster the development of endometriosis: a pilot study

Authors: Caihua Li, Zhimin Lu, Kaihuan Bi, Kangxia Wang, Yuping Xu, Peipei Guo, Ya Chen, Ping Zhou, Zhaolian Wei, Huanhuan Jiang, Yunxia Cao

Published in: Reproductive Biology and Endocrinology | Issue 1/2019

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Abstract

Background

Immune dysregulation is one of the mechanisms to promote endometriosis (EMS). Various T cell subpopulations have been reported to play different roles in the development of EMS. The mucosa-associated invariant T cell (MAIT) is an important T cell subset in the pathogenesis of various autoimmune diseases. Evidence has indicated that there are three functionally distinct MAIT subsets: CD4+, CD8+ and CD4/CD8−/− (double negative, DN) MAIT cells. Till now, the associations between endometriosis and MAIT have not been studied. Our research investigates different MAIT subpopulations in peripheral blood (PB) and peritoneal fluid (PF) from EMS patients.

Methods

Thirty-two EMS patients and eighteen controls were included. PB and PF were collected. Tests of cytokines in plasma and PF were performed by ELISA kit. Characterisations of MAIT were done by flow cytometry. MAIT cells have been defined as CD3 + CD161 + Vα7.2+ cells. Based on CD4 and CD8 expression, they were divided into CD8+MAIT, CD4+MAIT and DN MAIT.

Results

Enrichments of MAIT cells, especially CD4 and CD8 MAIT subsets were found. Moreover, CD8 MAIT cells had a high activation in the EMS group. EMS patients produced higher level of IL-8/12/17 as compared to these from controls. On the contrary, control patients exhibited an impressive upregulation of DN MAIT cells, however, these DN MAIT cells from controls showed a higher expression of PD-1. Lastly, we performed the relevance analysis, and discovered that the accumulation of PB MAIT cells positively correlated with an elevated level of serum CA125 production in EMS group.

Conclusion

These results suggest that different MAIT subsets play distinct roles in the progression of endometriosis.
Appendix
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Literature
1.
Vercellini P, Viganò P, Somigliana E, Fedele L. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. 2014;10:261–75.CrossRefPubMed
2.
3.
Leeners B, Damaso F, Ochsenbein-Kölble N, Farquhar C. The effect of pregnancy on endometriosis-facts or fiction? Hum Reprod Update. 2018;24:290–9.CrossRefPubMed
4.
5.
6.
Guo SW, Du Y, Liu X. Platelet-derived TGF-β1 mediates the down-modulation of NKG2D expression and may be responsible for impaired natural killer (NK) cytotoxicity in women with endometriosis. Hum Reprod. 2016;31:1462–74.CrossRefPubMed
7.
Symons LK, Miller JE, Kay VR, Marks RM, Liblik K, Koti M, Tayade C. The immunopathophysiology of endometriosis. Trends Mol Med. 2018;24:748–62.CrossRefPubMed
8.
Young VJ, Ahmad SF, Duncan WC, Horne AW. The role of TGF-β in the pathophysiology of peritoneal endometriosis. Hum Reprod Update. 2017;23:548–59.CrossRefPubMed
9.
Chen Y, Wang K, Xu Y, et al. Alteration of myeloid-derived suppressor cells, chronic inflammatory cytokines, and exosomal miRNA contribute to the peritoneal immune disorder of patients with endometriosis. Reprod Sci. 2018;19:1933719118808923.
10.
Zhang T, De Carolis C, Man GCW, Wang CC. The link between immunity, autoimmunity and endometriosis: a literature update. Autoimmun Rev. 2018;17:945–55.CrossRefPubMed
11.
Chen H, Qin S, Lei A, Li X, Gao Q, Dong J, Xiao Q, Zhou J. Expansion of monocytic myeloid-derived suppressor cells in endometriosis patients: a pilot study. Int Immunopharmacol. 2017;47:150–8.CrossRefPubMed
12.
Hanada T, Tsuji S, Nakayama M, Wakinoue S, Kasahara K, Kimura F, Mori T, Ogasawara K, et al. Suppressive regulatory T cells and latent transforming growth factor-β-expressing macrophages are altered in the peritoneal fluid of patients with endometriosis. Reprod Biol Endocrinol. 2018;16:9.CrossRefPubMedPubMedCentral
13.
Sun Y, Shao J, Jiang F, et al. CD33+CD14+CD11b+HLA-DR− monocytic myeloid-derived suppressor cells recruited and activated by CCR9/CCL25 are crucial for the pathogenic progression of endometriosis. Am J Reprod Immunol. 2019;81:e13067.CrossRefPubMed
14.
Barra F, Ferrero S. The role of monocytic myeloid-derived suppressor cells in the pathogenesis of endometriosis. Am J Reprod Immunol. 2019;81:e13094.CrossRefPubMed
15.
Arduini S, Dunne J, Conlon N, Feighery C, Doherty DG. Mucosal-associated invariant T cells are depleted and functionally altered in patients with common variable immunodeficiency. Clin Immunol. 2017;176:23–30.CrossRefPubMed
16.
Godfrey DI, Le Nours J, Andrews DM, Uldrich AP, Rossjohn J. Unconventional T cell targets for Cancer immunotherapy. Immunity. 2018;48:453–73.CrossRefPubMed
17.
Howson LJ, Napolitani G, Shepherd D, et al. MAIT cell clonal expansion and TCR repertoire shaping in human volunteers challenged with Salmonella Paratyphi a. Nat Commun. 2018;9:253.CrossRefPubMedPubMedCentral
18.
19.
McWilliam HEG, Villadangos JA. How MR1 presents a pathogen metabolic signature to mucosal-associated invariant T (MAIT) cells. Trends Immunol. 2017;38:679–89.CrossRefPubMed
20.
Gogacz M, Winkler I, Bojarska-Junak A, Tabarkiewicz J, Semczuk A, Rechberger T, Adamiak A. Increased percentage of Th17 cells in peritoneal fluid is associated with severity of endometriosis. J Reprod Immunol. 2016;117:39–44.CrossRefPubMed
21.
Yuan M, Li D, An M, Li Q, Zhang L, Wang G. Rediscovering peritoneal macrophages in a murine endometriosis model. Hum Reprod. 2017;32:94–102.CrossRefPubMed
22.
Yong YK, Saeidi A, Tan HY, et al. Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161(++) TCR iValpha7.2(+) Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection. Front Immunol. 2018;9:472.CrossRefPubMedPubMedCentral
23.
Coulter F, Parrish A, Manning D, et al. IL-17 production from T helper 17, mucosal-associated invariant T, and γδ cells in tuberculosis infection and disease. Front Immunol. 2017;8:1252.CrossRefPubMedPubMedCentral
24.
Rouxel O, Da Silva J, Beaudoin L, et al. Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes. Nat Immunol. 2017;18:1321–31.CrossRefPubMedPubMedCentral
25.
26.
Salou M, Nicol B, Garcia A, et al. Neuropathologic, phenotypic and functional analyses of Mucosal Associated Invariant T cells in Multiple Sclerosis. Clin Immunol. 2016;166–167:1–11.CrossRefPubMed
27.
Lezmi G, Abou Taam R, Dietrich C, Chatenoud L, de Blic J, Leite-de-Moraes M. Circulating IL-17-producing mucosal-associated invariant T cells (MAIT) are associated with symptoms in children with asthma. Clin Immunol. 2018;188:7–11.CrossRefPubMed
28.
Ayaz L, Çelik SK, Çayan F, Aras-Ateş N, Tamer L. Functional association of interleukin-18 gene −607 C/a promoter polymorphisms with endometriosis. Fertil Steril. 2011;95:298–300.CrossRefPubMed
29.
Magalhaes I, Pingris K, Poitou C, et al. Mucosal-associated invariant T cell alterations in obese and type 2 diabetic patients. J Clin Invest. 2015;125:1752–62.CrossRefPubMedPubMedCentral
30.
Gracey E, Qaiyum Z, Almaghlouth I, et al. IL-7 primes IL-17 in mucosal-associated invariant T (MAIT) cells, which contribute to the Th17-axis in ankylosing spondylitis. Ann Rheum Dis. 2016;75:2124–32.CrossRefPubMed
31.
32.
Shaler CR, Tun-Abraham ME, Skaro AI, Khazaie K, Corbett AJ, Mele T, Hernandez-Alejandro R, Haeryfar SMM. Mucosa-associated invariant T cells infiltrate hepatic metastases in patients with colorectal carcinoma but are rendered dysfunctional within and adjacent to tumor microenvironment. Cancer Immunol Immunother. 2017;66:1563–75.CrossRefPubMed
33.
Sundström P, Ahlmanner F, Akéus P, et al. Human mucosa-associated invariant T cells accumulate in Colon adenocarcinomas but produce reduced amounts of IFN-γ. J Immunol. 2015;195:3472–81.CrossRefPubMed
34.
Rudak PT, Choi J, Haeryfar SMM. MAIT cell-mediated cytotoxicity: roles in host defense and therapeutic potentials in infectious diseases and cancer. J Leukoc Biol. 2018;104:473–86.CrossRefPubMed
35.
Venken K, Favreau M, Gaublomme D, Menu E, Vanderkerken K, Elewaut D. Checkpoint inhibition in the treatment of multiple myeloma: a way to boost innate-like T cell anti-tumor function? Mol Immunol. 2018;101:521–6.CrossRefPubMed
36.
Shey MS, Balfour A, Wilkinson KA, Meintjes G. Contribution of APCs to mucosal-associated invariant T cell activation in infectious disease and cancer. Innate Immun. 2018;24:192–202.CrossRefPubMedPubMedCentral
37.
Haeryfar SMM, Shaler CR, Rudak PT. Mucosa-associated invariant T cells in malignancies: a faithful friend or formidable foe? Cancer Immunol Immunother. 2018;67:1885–96.CrossRefPubMed
38.
39.
American Society for Reproductive Medicine. Revised American society for reproductive medicine classification of endometriosis. Fertil Steril. 1997;67:817–21.CrossRef
40.
Sampson JA. Peritoneal endometriosis due to menstrual dissemination of endometrial tissues into the peritoneal cavity. Am J Obstet Gynaecol. 1927;14:422–69.CrossRef
41.
Mori L, Lepore M, De Libero G. The immunology of CD1- and MR1-restricted T cells. Annu Rev Immunol. 2016;34:479–510.CrossRefPubMed
42.
Chang KK, Liu LB, Jin LP, et al. IL-27 triggers IL-10 production in Th17 cells via a c-Maf/RORγt/Blimp-1 signal to promote the progression of endometriosis. Cell Death Dis. 2017;16:e2666.CrossRef
43.
Kurioka A, Jahun AS, Hannaway RF, et al. Shared and Distinct Phenotypes and Functions of Human CD161++ Valpha7.2+ T Cell Subsets. Front Immunol. 2017;8:1031.CrossRefPubMedPubMedCentral
44.
Dias J, Boulouis C, Gorin JB, et al. The CD4(−) CD8(−) MAIT cell subpopulation is a functionally distinct subset developmentally related to the main CD8(+) MAIT cell pool. Proc Natl Acad Sci U S A. 2018;115:E11513–22.CrossRefPubMedPubMedCentral
45.
Fergusson JR, Ussher JE, Kurioka A, Klenerman P, Walker LJ. High MDR-1 expression by MAIT cells confers resistance to cytotoxic but not immunosuppressive MDR-1 substrates. Clin Exp Immunol. 2018;194:180–91.CrossRefPubMedPubMedCentral
Metadata
Title
CD4+/CD8+ mucosa-associated invariant T cells foster the development of endometriosis: a pilot study
Authors
Caihua Li
Zhimin Lu
Kaihuan Bi
Kangxia Wang
Yuping Xu
Peipei Guo
Ya Chen
Ping Zhou
Zhaolian Wei
Huanhuan Jiang
Yunxia Cao
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2019
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-019-0524-5

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