Cooperation between IL-7 Receptor and Integrin alpha 2 beta 1 (CD49b) Drives Th17-Mediated Bone Loss

• Published in: The Journal of immunology (1950) Vol. 195; no. 9; pp. 4198 - 4209
• Main Authors: El Azreq, Mohammed-Amine, Arseneault, Claudie, Boisvert, Marc, Page, Nathalie, Allaeys, Isabelle, Poubelle, Patrice E, Tessier, Philippe A, Aoudjit, Fawzi
• Format: Journal Article
• Language: English
• Published: 01.11.2015
• ISSN: 0022-1767
• DOI: 10.4049/jimmunol.1500437

Th17 cells are critical effectors in inflammation and tissue damage such as bone erosion, but the mechanisms regulating their activation in this process are not fully understood. In this study, we considered the cooperation between cytokine receptors and integrin pathways in Th17-osteoclast function. We found that human Th17 cells coexpress IL-7R and the collagen-binding integrin alpha 2 beta 1 (CD49b), and IL-7 increases their adhesion to collagen via alpha 2 beta 1 integrin. In addition, coengagement of the two receptors in human Th17 cells cooperatively enhanced their IL-17 production and their osteoclastogenic function. The functional cooperation between IL-7R and alpha 2 beta 1 integrin involves activation of the JAK/PI3K/AKT (protein kinase B) and MAPK/ERK pathways. We also showed that IL-7-induced bone loss in vivo is associated with Th17 cell expansion. Moreover, blockade of alpha 2 beta 1 integrin with a neutralizing mAb inhibited IL-7-induced bone loss and osteoclast numbers by reducing Th17 cell numbers in the bone marrow and reducing the production of IL-17 and the receptor activator of NF- Kappa B ligand. Thus, the cooperation between IL-7R and alpha 2 beta 1 integrin can represent an important pathogenic pathway in Th17-osteoclast function associated with inflammatory diseases.