MDSCs drive the process of endometriosis by enhancing angiogenesis and are a new potential therapeutic target

Tao Zhang, Juhua Zhou, Gene Chi Wai Man, Kam Tong Leung, Bo Liang, Bo Xiao, Xinting Ma, Shaoyan Huang, Huaxiang Huang, Venkatesh L. Hegde, Yin Zhong, Yanmin Li, Grace Wing Shan Kong, Alice Ka Wah Yiu, Joseph Kwong, Pak Cheung Ng, Bruce A. Lessey, Prakash S. Nagarkatti, Mitzi Nagarkatti, Chi Chiu Wang

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1059-1073
Number of pages15
JournalEuropean Journal of Immunology
Volume48
Issue number6
DOIs
StatePublished - Jun 2018

Keywords

  • Angiogenesis
  • CXCR2
  • Endometriosis
  • Immunosuppression
  • Myeloid-derived suppressor cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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