Development, cytokine profile and function of human interleukin 17–producing helper T cells

Abstract

T(H)-17 cells are a distinct lineage of proinflammatory T helper cells that are essential for autoimmune disease. In mice, commitment to the T(H)-17 lineage is dependent on transforming growth factor-beta and interleukin 6 (IL-6). Here we demonstrate that IL-23 and IL-1beta induced the development of human T(H)-17 cells expressing IL-17A, IL-17F, IL-22, IL-26, interferon-gamma, the chemokine CCL20 and transcription factor RORgammat. In situ, T(H)-17 cells were identified by expression of the IL-23 receptor and the memory T cell marker CD45RO. Psoriatic skin lesions contained IL-23-producing dendritic cells and were enriched in the cytokines produced by human T(H)-17 cells that promote the production of antimicrobial peptides in human keratinocytes. Our data collectively indicate that human and mouse T(H)-17 cells require distinct factors during differentiation and that human T(H)-17 cells may regulate innate immunity in epithelial cells.

TLR2‐activated human langerhans cells promote Th17 polarization via IL‐1β, TGF‐β and IL‐23

“…In our study TGF-b was found to be spontaneously released, independent of any agonist. By detection of IL-1b, IL-6, IL-23, and TGF-b we found cytokines that recently have been proposed to be crucial for Th17 commitment [15][16][17][18][19]. However, even in human T cells, IL-23 seems to be responsible rather for enhancement than commitment of IL-17 [34], but in human CD8 1 T cells also IL-17 induction was observed [35].…”

“…In mice, TGF-b together with IL-6 [15], with IL-23 [16], or with IL-6 and TNF-a [17] were reported to drive the Th17 cell fate. In humans, IL-1b and IL-6 [18] or IL-23 and IL-1b [19] were observed to be crucial for Th17 commitment. The question, which cells are producing these Th17 differentiation factors, is under discussion as well.…”

“…4C). Based on investigations showing Th17 polarization by adding differentiating cytokines in the absence of antigen-presenting cells [16][17][18][19], we examined whether IL-6 and TGF-b could enhance the secretion of IL-17 in CD4 1 T cells. Interestingly, supplement of external IL-6 and TGF-b to the cocultures reduced the potential to secrete IL-17 at stimulation by PGN, synthetic lipopeptides, and LPS in CD1c 1 MoLC and CD1c 1 MoDC (Fig.…”

Overexpression of RORγt under control of the CD2 promoter induces polyclonal plasmacytosis and autoantibody production in transgenic mice

“…Expression of the transcription factor retinoic acid related orphan receptor gamma-t (RORγt) is required for the differentiation of Th17 cells [5,6]. The orphan receptor RORγt is a thymusspecific isoform of RORγ [7].…”

“…Th17 cells have been shown to participate in the development of autoimmunity, and also to play an important role in host defense against infection [4]. Expression of the transcription factor retinoic acid related orphan receptor gamma-t (RORγt) is required for the differentiation of Th17 cells [5,6]. The orphan receptor RORγt is a thymusspecific isoform of RORγ [7].…”