Mass cytometry analysis reveals a distinct immune environment in peritoneal fluid in endometriosis: a characterisation study

被引:66
作者
Guo, Manman [1 ]
Bafligil, Cemsel [1 ]
Tapmeier, Thomas [2 ]
Hubbard, Carol [2 ]
Manek, Sanjiv [2 ]
Shang, Catherine [2 ]
Martinez, Fernando O. [1 ]
Schmidt, Nicole [3 ]
Obendorf, Maik [3 ]
Hess-Stumpp, Holger [3 ]
Zollner, Thomas M. [3 ]
Kennedy, Stephen [2 ]
Becker, Christian M. [2 ]
Zondervan, Krina T. [2 ,4 ]
Cribbs, Adam P. [1 ]
Oppermann, Udo [1 ,5 ]
机构
[1] Univ Oxford, Botnar Res Ctr, NIHR Biomed Res Unit Oxford, Nuffield Dept Musculoskeletal Sci, Oxford, England
[2] Univ Oxford, Nuffield Dept Womens & Reprod Hlth, Oxford, England
[3] Bayer AG, Drug Discovery Pharmaceut, Gynecol Therapies, Mullerstr 178, Berlin, Germany
[4] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England
[5] Univ Freiburg, Freiburg Inst Adv Studies FRIAS, Freiburg, Germany
关键词
Endometriosis; Mass cytometry; Peritoneal fluid; Peripheral blood; Immune cells; Innate immunity; Adaptive immunity; CD69; KILLER-CELL ACTIVITY; DENDRITIC CELLS; MACROPHAGE ACTIVATION; SURFACE-MARKERS; EXPRESSION; MONOCYTES; GROWTH; WOMEN; ASSOCIATION; PHENOTYPE;
D O I
10.1186/s12916-019-1470-y
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Endometriosis is a gynaecological condition characterised by immune cell infiltration and distinct inflammatory signatures found in the peritoneal cavity. In this study, we aim to characterise the immune microenvironment in samples isolated from the peritoneal cavity in patients with endometriosis. Methods We applied mass cytometry (CyTOF), a recently developed multiparameter single-cell technique, in order to characterise and quantify the immune cells found in peritoneal fluid and peripheral blood from endometriosis and control patients. Results Our results demonstrate the presence of more than 40 different distinct immune cell types within the peritoneal cavity. This suggests that there is a complex and highly heterogeneous inflammatory microenvironment underpinning the pathology of endometriosis. Stratification by clinical disease stages reveals a dynamic spectrum of cell signatures suggesting that adaptations in the inflammatory system occur due to the severity of the disease. Notably, among the inflammatory microenvironment in peritoneal fluid (PF), the presence of CD69(+) T cell subsets is increased in endometriosis when compared to control patient samples. On these CD69(+) cells, the expression of markers associated with T cell function are reduced in PF samples compared to blood. Comparisons between CD69(+) and CD69(-) populations reveal distinct phenotypes across peritoneal T cell lineages. Taken together, our results suggest that both the innate and the adaptive immune system play roles in endometriosis. Conclusions This study provides a systematic characterisation of the specific immune environment in the peritoneal cavity and identifies cell immune signatures associated with endometriosis. Overall, our results provide novel insights into the specific cell phenotypes governing inflammation in patients with endometriosis. This prospective study offers a useful resource for understanding disease pathology and opportunities for identifying therapeutic targets.
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页数:16
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共 69 条
[21]  
DHooghe TM, 1996, HUM REPROD, V11, P1736
[22]   ANTIENDOMETRIAL LYMPHOCYTOTOXICITY AND NATURAL-KILLER-CELL ACTIVITY IN BABOONS (PAPIO-ANUBIS AND PAPIO-CYNOCEPHALUS) WITH ENDOMETRIOSIS [J].
DHOOGHE, TM ;
SCHEERLINCK, JPY ;
KONINCKX, PR ;
HILL, JA ;
BAMBRA, CS .
HUMAN REPRODUCTION, 1995, 10 (03) :558-562
[23]   Aberrant expression of CD95 and CD69 molecules among CD56+ cells in women with endometriosis [J].
Eidukaite, A ;
Siaurys, A ;
Tamosiunas, V .
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 2006, 55 (04) :276-281
[24]   Is there an association between autoimmunity and endometriosis? [J].
Eisenberg, Vered H. ;
Zolti, Mati ;
Soriano, David .
AUTOIMMUNITY REVIEWS, 2012, 11 (11) :806-814
[25]   Dendritic cells support angiogenesis and promote lesion growth in a murine model of endometriosis [J].
Fainaru, Ofer ;
Adini, Avner ;
Benny, Ofra ;
Adini, Irit ;
Short, Sarah ;
Bazinet, Lauren ;
Nakai, Kei ;
Pravda, Elke ;
Hornstein, Mark D. ;
D'Amato, Robert J. ;
Folkman, Judah .
FASEB JOURNAL, 2008, 22 (02) :522-529
[26]   CD161 Defines a Transcriptional and Functional Phenotype across Distinct Human T Cell Lineages [J].
Fergusson, Joannah R. ;
Smith, Kira E. ;
Fleming, Vicki M. ;
Rajoriya, Neil ;
Newell, Evan W. ;
Simmons, Ruth ;
Marchi, Emanuele ;
Bjorkander, Sophia ;
Kang, Yu-Hoi ;
Swadling, Leo ;
Kurioka, Ayako ;
Sahgal, Natasha ;
Lockstone, Helen ;
Baban, Dilair ;
Freeman, Gordon J. ;
Sverremark-Ekstrom, Eva ;
Davis, Mark M. ;
Davenport, Miles P. ;
Venturi, Vanessa ;
Ussher, James E. ;
Willberg, Christian B. ;
Klenerman, Paul .
CELL REPORTS, 2014, 9 (03) :1075-1088
[27]   Monocyte and macrophage heterogeneity [J].
Gordon, S ;
Taylor, PR .
NATURE REVIEWS IMMUNOLOGY, 2005, 5 (12) :953-964
[28]   Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny [J].
Guilliams, Martin ;
Ginhoux, Florent ;
Jakubzick, Claudia ;
Naik, Shalin H. ;
Onai, Nobuyuki ;
Schraml, Barbara U. ;
Segura, Elodie ;
Tussiwand, Roxane ;
Yona, Simon .
NATURE REVIEWS IMMUNOLOGY, 2014, 14 (08) :571-578
[29]   CD69+CD4+CD25- T Cells, a New Subset of Regulatory T Cells, Suppress T Cell Proliferation through Membrane-Bound TGF-β1 [J].
Han, Yanmei ;
Guo, Qiuli ;
Zhang, Minggang ;
Chen, Zhubo ;
Cao, Xuetao .
JOURNAL OF IMMUNOLOGY, 2009, 182 (01) :111-120
[30]  
HILL JA, 1988, FERTIL STERIL, V50, P216