Deficient SOCS3 expression in CD4+CD25+FoxP3+ regulatory T cells and SOCS3‐mediated suppression of Treg function
Open Access
- 26 July 2007
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 37 (8), 2082-2089
- https://doi.org/10.1002/eji.200737193
Abstract
Naturally occurring CD4+CD25+FoxP3+ regulatory T cells (Treg) suppress T helper (Th) cell‐mediated immune responses. The cytokines IL‐2 and IL‐6 are known to influence Treg function. However, their relative effects on Th cells versus Treg are not well understood. Stimulation with IL‐2, and to a lesser extent, IL‐6, enhanced Treg proliferation, FoxP3 and CTLA4 maintenance, and suppressive function. In contrast, when IL‐2 or IL‐6 were added to Treg/Th cell cocultures, suppression was inhibited. The molecule SOCS3 negatively regulates responses to IL‐2 and IL‐6. Interestingly, unlike Th cells, Treg were found to be deficient in SOCS3 protein expression. The significance of this finding lies in the need for Treg to rapidly respond to these cytokines to prevent unwarranted immune responses to self‐antigens. Overexpression of SOCS3 in Treg decreased their proliferation, FoxP3 and CTLA‐4 expression and suppressive function. Thus, up‐regulation of SOCS3 expression may be a useful therapeutic approach in diseases where inhibition of Treg is desirable.Keywords
This publication has 46 references indexed in Scilit:
- Cutting Edge: Decreased Accumulation and Regulatory Function of CD4+CD25high T Cells in Human STAT5b DeficiencyThe Journal of Immunology, 2006
- The role of CD28 and cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) in regulatory T‐cell biologyImmunological Reviews, 2006
- FOXP3: Of Mice and MenAnnual Review of Immunology, 2006
- The IL-6R α chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivoJCI Insight, 2005
- Cutting Edge: IL-2 Is Critically Required for the In Vitro Activation of CD4+CD25+ T Cell Suppressor FunctionThe Journal of Immunology, 2004
- Activation requirements for the induction of CD4+CD25+ T cell suppressor functionEuropean Journal of Immunology, 2004
- Control of Regulatory T Cell Development by the Transcription Factor Foxp3Science, 2003
- Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouseNature Genetics, 2001
- JM2, encoding a fork head–related protein, is mutated in X-linked autoimmunity–allergic disregulation syndromeJCI Insight, 2000
- Immunologic Self-Tolerance Maintained by Cd25+Cd4+Regulatory T Cells Constitutively Expressing Cytotoxic T Lymphocyte–Associated Antigen 4The Journal of Experimental Medicine, 2000