Cutting edge: Generation of colitogenic Th17 CD4 T cells is enhanced by IL-17+ γδ T cells.

Cutting Edge: Generation of Colitogenic Th17 CD4 T Cells Is Enhanced by IL-17 gd T Cells

CD4 T cells play important roles in maintaining IL-17-producing γδ T cell subsets in naïve animals

A proportional balance between αβ and γδ T-cell subsets in the periphery is exceedingly well maintained by a homeostatic mechanism. However, a cellular mechanism underlying the regulation remains undefined. We recently reported that a subset of developing γδ T cells spontaneously acquires interleukin (IL)-17-producing capacity even within naive animals through a transforming growth factor (TGF)...

Cutting edge: Alternative signaling of Th17 cell development by sphingosine 1-phosphate.

Sphingosine 1-phosphate (S1P) in blood and lymph controls T cell traffic and proliferation through type 1 S1P receptor (S1P(1)) signals, but suppression of IFN-gamma generation has been the only consistently observed effect on T cell cytokines. The fact that S1P enhances the development of Th17 cells from Ag-challenged transgenic S1P(1)-overexpressing CD4 T cells suggested that the S1P-S1P(1) a...

SerpinB1 regulates homeostatic expansion of IL-17+ γδ and CD4+ Th17 cells.

SerpinB1 is an endogenous inhibitor of serine proteases recognized for its anti-inflammatory and host-protective properties. Although loss of serpinB1 in mice does not result in gross immune deregulation, serpinb1a(-/-) mice display increased mortality and inflammation-associated morbidity upon challenge with influenza virus. Here, we show that IL-17A(+) γδ and CD4(+) Th17 cells are already exp...

Th17 cells, not IL-17+ γδ T cells, drive arthritic bone destruction in mice and humans.

The mechanism whereby IL-17 drives rheumatoid arthritis remains incompletely understood. We demonstrate that anti-IL-17 therapy in collagen-induced arthritis ameliorates bone damage by reducing the number of osteoclasts in joints. We found equal numbers of CD4(+) Th17 and IL-17 producing γδ T cells in the joints of arthritic mice, and in vitro, both populations similarly induced osteoclastogene...