Interleukin-10 deficiency impairs regulatory T cell-derived neuropilin-1 functions and promotes Th1 and Th17 immunity.

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.

• Authors: Shimin Wang, Xiang Gao, Guobo Shen, Wei Wang, Jingyu Li, Jingyi Zhao, Yu-Quan Wei, Carl K Edwards
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 24249 (Apr 14 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27075020 (Publication Type: Journal Article)

Chemical References

• Interleukin-10
• Neuropilin-1

Topics

• Animals
• Interleukin-10 (deficiency)
• Mice, Inbred C57BL
• Mice, Knockout
• Neuropilin-1 (metabolism)
• T-Lymphocytes, Regulatory (metabolism)
• Th1 Cells (immunology)
• Th17 Cells (immunology)