FOXP3 and the regulation of Treg/Th17 differentiation.
CD4 T cell lineages are marked by the signature transcription factor each lineage expresses. For example, regulatory T cells (Tregs) are characterized by expression of FOXP3, which is either induced during thymic development for natural Tregs (nTregs), or in the periphery in the presence of TGF-beta and retinoic acid for induced Tregs (iTreg). Interestingly, recent work has shown that the signature transcription factor for Th17 cells, RORgammat, is also induced by TGF-beta, thus linking the differentiation of the Treg and Th17 lineages. In the absence of a second signal from a proinflammatory cytokine, FOXP3 can inhibit RORgammat function and drive Treg differentiation. However, when the cell also receives a signal from a proinflammation cytokine (e.g., IL-6), FOXP3 function is inhibited and the Th17 differentiation pathway is induced. Therefore, it is the balance between FOXP3 and RORgammat function that determines CD4 T cell fate and the type of immune response that will be generated.
Ziegler
Steven F
SF
Immunology, Benaroya Research Institute, Seattle, WA 98101, USA. sziegler@benaroyaresearch.org
Buckner
Jane H
JH
D002454:Cell Differentiation; D051858:Forkhead Transcription Factors / Q000502:physiology*; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid / Q000502:physiology; D011988:Receptors, Thyroid Hormone / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone