TGFbeta and retinoic acid intersect in immune-regulation.
Transforming growth factor (TGFbeta) prevents T(H)1 and T(H)2 differentiation and converts naïve CD4 cells into Foxp3-expressing T regulatory (Treg) cell.(1,2) In sharp contrast, in the presence of pro-inflammatory cytokines, including IL-6, TGFbeta not only inhibits Foxp3 expression but also promotes the differentiation of pro-inflammatory IL17-producing CD4 effector T (T(H)17) cells.(3-5) This reciprocal TGFbeta-dependent differentiation imposes a critical dilemma between pro- and anti-inflammatory immunity and suggests that a sensitive regulatory mechanism must exist to control TGFbeta-driven T(H)17 effector and Treg differentiation. A vitamin A metabolite, retinoic acid (RA), was recently identified as a key modulator of TGFbeta-driven- immune deviation capable of suppressing T(H)17 differentiation while promoting Foxp3(+)Treg generation.(6-10).
Mucida
Daniel
D
La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
Cheroutre
Hilde
H
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology*; D014212:Tretinoin / Q000276:immunology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508600:IL6 protein, human; D020381:Interleukin-17; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014212:Tretinoin