TY - JOUR
T1 - MDSCs drive the process of endometriosis by enhancing angiogenesis and are a new potential therapeutic target
AU - Zhang, Tao
AU - Zhou, Juhua
AU - Man, Gene Chi Wai
AU - Leung, Kam Tong
AU - Liang, Bo
AU - Xiao, Bo
AU - Ma, Xinting
AU - Huang, Shaoyan
AU - Huang, Huaxiang
AU - Hegde, Venkatesh L.
AU - Zhong, Yin
AU - Li, Yanmin
AU - Kong, Grace Wing Shan
AU - Yiu, Alice Ka Wah
AU - Kwong, Joseph
AU - Ng, Pak Cheung
AU - Lessey, Bruce A.
AU - Nagarkatti, Prakash S.
AU - Nagarkatti, Mitzi
AU - Wang, Chi Chiu
N1 - © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2018/6
Y1 - 2018/6
N2 - Endometriosis affects women of reproductive age via unclear immunological mechanism(s). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid cells with potent immunosuppressive and angiogenic properties. Here, we found MDSCs significantly increased in the peripheral blood of patients with endometriosis and in the peritoneal cavity of a mouse model of surgically induced endometriosis. Majority of MDSCs were granulocytic, produced ROS, and arginase, and suppressed T-cell proliferation. Depletion of MDSCs by antiGr-1 antibody dramatically suppressed development of endometrial lesions in mice. The chemokines CXCL1, 2, and 5 were expressed at sites of lesion while MDSCs expressed CXCR-2. These CXC-chemokines promoted MDSC migration toward endometriotic implants both in vitro and in vivo. Also, CXCR2-deficient mice show significantly decreased MDSC induction, endometrial lesions, and angiogenesis. Importantly, adoptive transfer of MDSCs into CXCR2-KO mice restored endometriotic growth and angiogenesis. Together, this study demonstrates that MDSCs play a role in the pathogenesis of endometriosis and identifies a novel CXC-chemokine and receptor for the recruitment of MDSCs, thereby providing a potential target for endometriosis treatment.
AB - Endometriosis affects women of reproductive age via unclear immunological mechanism(s). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid cells with potent immunosuppressive and angiogenic properties. Here, we found MDSCs significantly increased in the peripheral blood of patients with endometriosis and in the peritoneal cavity of a mouse model of surgically induced endometriosis. Majority of MDSCs were granulocytic, produced ROS, and arginase, and suppressed T-cell proliferation. Depletion of MDSCs by antiGr-1 antibody dramatically suppressed development of endometrial lesions in mice. The chemokines CXCL1, 2, and 5 were expressed at sites of lesion while MDSCs expressed CXCR-2. These CXC-chemokines promoted MDSC migration toward endometriotic implants both in vitro and in vivo. Also, CXCR2-deficient mice show significantly decreased MDSC induction, endometrial lesions, and angiogenesis. Importantly, adoptive transfer of MDSCs into CXCR2-KO mice restored endometriotic growth and angiogenesis. Together, this study demonstrates that MDSCs play a role in the pathogenesis of endometriosis and identifies a novel CXC-chemokine and receptor for the recruitment of MDSCs, thereby providing a potential target for endometriosis treatment.
KW - Angiogenesis
KW - CXCR2
KW - Endometriosis
KW - Immunosuppression
KW - Myeloid-derived suppressor cells
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U2 - 10.1002/eji.201747417
DO - 10.1002/eji.201747417
M3 - Article
C2 - 29460338
AN - SCOPUS:85043576435
VL - 48
SP - 1059
EP - 1073
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 6
ER -