title: 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.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Shimin
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, PR China.|Institute of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Guobo
authors.initials: G
authors.lastname: Shen
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wei
authors.affiliation: Department of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Carl K
authors.initials: CK
authors.lastname: Edwards
mesh_terms: D000818:Animals; D016753:Interleukin-10 / Q000172:deficiency*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039942:Neuropilin-1 / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D016753:Interleukin-10; D039942:Neuropilin-1