PMID:22079196

Citation	Sun, L, Wu, J and Yi, S (2012) Foxp3 is critical for human natural CD4+CD25+ regulatory T cells to suppress alloimmune response. Transpl. Immunol. 26:71-80
Abstract	Naturally occurring CD4+CD25+ regulatory T cells (nTregs) that express high level of Foxp3 actively suppress pathological and physiological immune responses, contributing to the maintenance of immunological self-tolerance and immune homeostasis. Although Foxp3 is required for nTreg development and appears to be necessary for mature murine Treg function, the precise role of Foxp3 in regulating natural human Treg function in alloimmune response is unclear. In this study, we used siRNA-mediated gene silencing to knockdown Foxp3 expression in natural human Tregs and investigated the importance of Foxp3 in maintaining human nTreg suppressive function. We showed that Foxp3 knockdown resulted in impaired phenotype and nonresponsiveness, downregulated expression of function molecules, and reduced production of suppressive cytokines in nTregs. These changes correlated with diminished nTreg activity in suppressing proliferation of effector CD4+CD25- T cells, their cytotoxicity against allogeneic target cells and production of effector cytokines in response to allogeneic stimulation. Thus, this study shows that ongoing Foxp3 expression is required for natural human Tregs to maintain their phenotype and suppressive function in the alloimmune response.
Links	PubMed Online version:10.1016/j.trim.2011.10.005
Keywords	Animals; Cell Proliferation; Female; Forkhead Transcription Factors/biosynthesis; Forkhead Transcription Factors/genetics; Forkhead Transcription Factors/immunology; Gene Expression Regulation/genetics; Gene Expression Regulation/immunology; Gene Silencing/immunology; Humans; Male; Mice; RNA, Small Interfering/genetics; Self Tolerance; T-Lymphocytes, Regulatory/cytology; T-Lymphocytes, Regulatory/immunology; T-Lymphocytes, Regulatory/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:B7ZLG1		GO:0001819: positive regulation of cytokine production	ECO:0000315:		P		Fig. 5	complete CACAO 2979
HUMAN:B7ZLG1		GO:0002361: CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	ECO:0000315:		P		Fig. 2	complete CACAO 2980
HUMAN:B7ZLG1	involved_in	GO:0002361: CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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