Alpha2beta1 integrin is the major collagen-binding integrin expressed on human Th17 cells

Growing evidence indicates that collagen-binding integrins are important costimulatory molecules of effector T cells. In this study, we demonstrate that the major collagen-binding integrin expressed by human Th17 cells is alpha2betal (alpha 2/beta 1) or VLA-2, also known as the receptor for collagen I on T cells. Our results show that human naive CD4(+) T cells cultured under Th17 polarization conditions preferentially upregulate alpha 2 beta 1 integrin rather than alpha 1 beta 1 integrin, which is the receptor for collagen IV on T cells. Double staining analysis for integrin receptors and intracellular IL-17 showed that alpha 2 integrin but not alpha 1 integrin is associated with Th17 cells. Cell adhesion experiments demonstrated that Th17 cells attach to collagen I and collagen II using alpha 2 beta 1 integrin but did not attach to collagen IV. Functional studies revealed that collagens I and II but not collagen IV costimulate the production of IL-17A, IL-17F and IFN-gamma by human Th17 cells activated with anti-CD3. These results identify alpha 2 beta 1 integrin as the major collagen receptor expressed on human Th17 cells and suggest that it can be an important costimulatory molecule of Th17 cell responses.