SOCS1 Is a Key Molecule That Prevents Regulatory T Cell Plasticity under Inflammatory Conditions - PubMed (original) (raw)

. 2017 Jul 1;199(1):149-158.

doi: 10.4049/jimmunol.1600441. Epub 2017 May 26.

Affiliations

• PMID: 28550203
• DOI: 10.4049/jimmunol.1600441

SOCS1 Is a Key Molecule That Prevents Regulatory T Cell Plasticity under Inflammatory Conditions

Reiko Takahashi et al. J Immunol. 2017.

Abstract

We previously showed that regulatory T cells (Tregs) from T cell-specific _Socs1_-deficient mice (Socs1fl/flLck-Cre+ mice) easily convert into Th1- or Th17-like cells (ex-Tregs), which lose Foxp3 expression and suppressive functions in vivo. Because Tregs in Socs1fl/flLck-Cre+ mice are constantly exposed to a large amount of inflammatory cytokines produced by non-Tregs in vivo, in this study we analyzed Treg-specific _Socs1_-deficient mice (Socs1fl/flFoxp3YFP-Cre mice). These mice developed dermatitis, splenomegaly, and lymphadenopathy that were much milder than those in Socs1fl/flLck-Cre+ mice. A fate mapping study revealed that Socs1 deficiency accelerated the conversion of Tregs to Foxp3-IFN-γ+ ex-Tregs in the tumor microenvironment and suppressed tumor growth. When transferred into _Rag2_-/- mice, Tregs from Socs1fl/flLck-Cre+ mice easily lost Foxp3 expression, whereas those from Socs1fl/flFoxp3YFP-Cre mice maintained Foxp3 expression. Although Tregs from Socs1fl/flLck-Cre+ mice produced IFN-γ after a 3-d culture in response to anti-CD3/CD28 Ab stimulation in vitro, Tregs from Socs1fl/flFoxp3YFP-Cre mice did not. This finding suggested that the inflammatory conditions in Socs1fl/flLck-Cre+ mice modified the born nature of _Socs1_-deficient Tregs. To investigate this mechanism, Tregs from Socs1fl/flFoxp3YFP-Cre mice were cultured with APCs from Socs1fl/flLck-Cre+ mice. These APCs facilitated STAT4 phosphorylation, IFN-γ production, and loss of Foxp3 expression in Tregs from Socs1fl/flFoxp3YFP-Cre mice in an IL-12-dependent manner. The results indicate that _Socs1_-deficient Tregs tend to convert into ex-Tregs under the inflammatory conditions in which APCs are highly activated, and that SOCS1 could be a useful target for enhancement of anti-tumor immunity.

Copyright © 2017 by The American Association of Immunologists, Inc.

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