A study of MDSC mediated immunosuppression in endometriosis
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摘要Endometriosis is a chronic disorder characterized by presence of endometrium outside the uterine cavity. In healthy women, the ectopic endometrial cells are normally eliminated by physiological immune surveillance. In women with endometriosis, the immune cells are not able to eradicate the ectopic endometrial cells, but facilitate and promote their survival and growth. The endometrium immune escape mediated by abnormal suppressive activities of the immune cells has been reported but the underlying mechanism are not well defined yet. Myeloid-derived suppressor cells (MDSCs) are a population of suppressive cells negatively regulate immune responses in cancer and other diseases, but MSDCs in endometriosis have not been studied before. Here we find that mouse CD11b+Gr1+ and human HLA-DRCD11b+ CD33+ MDSCs are increased in our experimental endometriosis model in mice and
endometriosis patients. Notably the evaluated mouse endometriosis CD11b+Gr1+ MDSCs also exhibit suppressive T cell response, arginase activity, reactive oxygen species production. In contrast, the mouse endometriosis MDSCs mainly expand transiently in peritoneum, but not in bone marrow and spleen; and present with distinct chemotaxic
profiles, including IL1/2R/3/4/6 cytokines and CXCL1/2 chemokines. Further we demonstrate that depletion of the mouse endometriosis CD11b+Gr1+ MDSCs by anti-Gr1 antibody inhibit the growth and development of the ndometriotic lesions in mice. Given that MDSCs contribute to negative regulation of immune responses and promote progression of cancer and other pathological conditions via STATs signalling. Based on our findings, we proposed endometriosis MDSCs negatively regulate the immune responses and promote the growth and development of endometriosis; and the underlying mechanism involves IL1/2R/3/4/6- and CXCL1/2-mediate induction of STATs, in turn suppress the immune surveillance in endometriosis.
Endometriosis is a common gynaecological disorder mainly involve locally in peritoneal cavity with unclear immunological pathophysiology and modulation. Studying the endometriosis MDSCs will shed lights to understand the underlying mechanism of the endometrium immune escape in the development of the endometriosis. In long run, our study may also develop the endometriosis MDSC subsets and associated chemotaxic molecules as potential diagnostic marker for prediction and prognosis of the condition and possible therapeutic target for the treatment of endometriosis.
著者Zhang Tao, Kwong Joseph, Wang Chi Chiu
會議名稱Croucher Summer Course 2016, Advances in Immunology in Health and Disease
會議開始日16.08.2016
會議完結日20.08.2016
會議地點Hong Kong
會議國家/地區中國
出版年份2016
語言美式英語

上次更新時間 2018-23-01 於 03:21