Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells.

Abstract

Interleukin 17 (IL-17)-producing CD4(+) helper T cells (T(H)-17 cells) have been linked to host defense and autoimmune diseases. In mice, the differentiation of T(H)-17 cells requires transforming growth factor-beta and IL-6 and the transcription factor RORgammat. We report here that for human naive CD4(+) T cells, RORgammat expression and T(H)-17 polarization were induced by IL-1beta and enhanced by IL-6 but were suppressed by transforming growth factor-beta and IL-12. Monocytes and conventional dendritic cells, but not monocyte-derived dendritic cells activated by microbial stimuli, efficiently induced T(H)-17 priming, and this function correlated with antigen-presenting cell production of IL-1beta and IL-6 but not IL-12. Our results identify cytokines, antigen-presenting cells and microbial products that promote the polarization of human T(H)-17 cells and emphasize an important difference in the requirements for the differentiation of T(H)-17 cells in humans and mice.

• Authors: Eva V Acosta-Rodriguez, Giorgio Napolitani, Antonio Lanzavecchia, Federica Sallusto
• Journal: Nature immunology (Nat Immunol) Vol. 8 Issue 9 Pg. 942-9 (Sep 2007) ISSN: 1529-2908 [Print] United States
• PMID: 17676045 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Interleukin-17
• Interleukin-1beta
• Interleukin-6
• Nuclear Receptor Subfamily 1, Group F, Member 3
• RORC protein, human
• Receptors, Retinoic Acid
• Receptors, Thyroid Hormone
• Rorc protein, mouse
• Transforming Growth Factor beta
• Interleukin-12

Topics

• Antigen-Presenting Cells (immunology)
• Cell Differentiation (immunology)
• Cell Lineage (immunology)
• Cells, Cultured
• Cytokines (immunology, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Humans
• Interleukin-12 (metabolism)
• Interleukin-17 (biosynthesis)
• Interleukin-1beta (metabolism)
• Interleukin-6 (metabolism)
• Nuclear Receptor Subfamily 1, Group F, Member 3
• Receptors, Retinoic Acid (metabolism)
• Receptors, Thyroid Hormone (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• T-Lymphocyte Subsets (cytology, metabolism)
• T-Lymphocytes, Helper-Inducer (cytology, immunology)
• Transforming Growth Factor beta (metabolism)