Interleukin-10 Deficiency Impairs Regulatory T Cell-derived Neuropilin-1 Functions and Promotes Th1 and Th17 Immunity

Overview

Journal Sci Rep

Specialty Science

Date 2016 Apr 15

PMID 27075020

Citations 41

Authors

Shimin Wang

Xiang Gao

Guobo Shen

Wei Wang

Jingyu Li

Jingyi Zhao

Yu-quan Wei

Carl K Edwards

Affiliations

Soon will be listed here.

Abstract

Regulatory T cells (Tregs) expand in peripheral lymphoid organs and can produce immunosuppressive cytokines to support tumor growth. IL-10 abrogation efficiently induces Treg formation but dampens tumoral neuropilin-1 (Nrp-1) Treg signaling, which simultaneously augments Th1 and Th17 immunity. These effects are associated with the plasticity and stability of Tregs and effector T cell functions that can limit tumorigenesis. Within the tumor microenvironment, there appears to be a "mutual antagonism" between immunoenhancement and immunosuppression mechanisms, eventually leading to decreased metastasis. In contrast, tumor progression is paralleled by a reduction in Nrp-1-producing Tregs controlled by the IL-10 and TGF-β1 levels. However, Th1, Th17 and Treg immunity is primarily regulated by IL-10 or Nrp-1 and not TGF-β1 except when combined with IL-10. These results emphasize the important implications for the therapeutic use of Tregs. The number of Treg cells must be maintained in a healthy and dynamic homeostatic range to prevent malignant diseases. Moreover, Treg-mediated immunosuppression can be limited by reducing tumor-derived Treg Nrp-1 levels.

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