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 alpha2beta1 (α2β1) or VLA-2, also known as the receptor for collagen I on T cells. Our results show that human naïve CD4(+) T cells cultured under Th17 polarization conditions preferentially upregulate α2β1 integrin rather than α1β1 integrin, which is the receptor for collagen IV on T cells. Double staining analysis for integrin receptors and intracellular IL-17 showed that α2 integrin but not α1 integrin is associated with Th17 cells. Cell adhesion experiments demonstrated that Th17 cells attach to collagen I and collagen II using α2β1 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-γ by human Th17 cells activated with anti-CD3. These results identify α2β1 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.
Boisvert
Marc
M
Centre de Recherche en Rhumatologie/Immunologie, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, and Faculté de Médecine, Université Laval, Québec, Canada.
Chetoui
Nizar
N
Gendron
Steve
S
Aoudjit
Fawzi
F
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D003094:Collagen / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D038982:Integrin alpha2beta1 / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D038981:Receptors, Collagen / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D038982:Integrin alpha2beta1; D020381:Interleukin-17; D038981:Receptors, Collagen; D007371:Interferon-gamma; D003094:Collagen