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The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat.
Manel, Nicolas; Unutmaz, Derya; Littman, Dan R.
Afiliação
  • Manel N; The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.
Nat Immunol ; 9(6): 641-9, 2008 Jun.
Article em En | MEDLINE | ID: mdl-18454151
T(H)-17 cells are interleukin 17 (IL-17)-secreting CD4+ T helper cells involved in autoimmune disease and mucosal immunity. In naive CD4+ T cells from mice, IL-17 is expressed in response to a combination of IL-6 or IL-21 and transforming growth factor-beta (TGF-beta) and requires induction of the nuclear receptor RORgammat. It has been suggested that the differentiation of human T(H)-17 cells is independent of TGF-beta and thus differs fundamentally from that in mice. We show here that TGF-beta, IL-1beta and IL-6, IL-21 or IL-23 in serum-free conditions were necessary and sufficient to induce IL-17 expression in naive human CD4+ T cells from cord blood. TGF-beta upregulated RORgammat expression but simultaneously inhibited its ability to induce IL-17 expression. Inflammatory cytokines relieved this inhibition and increased RORgammat-directed IL-17 expression. Other gene products detected in T(H)-17 cells after RORgammat induction included the chemokine receptor CCR6, the IL-23 receptor, IL-17F and IL-26. Our studies identify RORgammat as having a central function in the differentiation of human T(H)-17 cells from naive CD4+ T cells and suggest that similar cytokine pathways are involved in this process in mice and humans.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores dos Hormônios Tireóideos / Células-Tronco Hematopoéticas / Diferenciação Celular / Fator de Crescimento Transformador beta / Receptores do Ácido Retinoico / Interleucina-17 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2008 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores dos Hormônios Tireóideos / Células-Tronco Hematopoéticas / Diferenciação Celular / Fator de Crescimento Transformador beta / Receptores do Ácido Retinoico / Interleucina-17 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2008 Tipo de documento: Article