Frontline Science: Human bone cells as a source of IL-27 under inflammatory conditions: role of TLRs and cytokines

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

Vacher-Lavenu, Marie-Cé¹  rie¹  Dumaine, Valé³  Anract, Philippe³  Devergne, Odile⁵  Audebourg, Anne⁶  re, Brigitte⁷  Bsiri, Laura⁷  Dietrich, Cé⁸  cile⁹  line^1,10  Radenen-Bussiè^1,11 

[1] Paris Descartes, HôParis Descartes, Paris, France;and;HP and UniversitéHP, HôINSERM U1151 CNRS UMR 8253, UniversitéService de Chirurgie OrthopéService de Pathologie, AP‐dique, AP‐pital Cochin, Paris, France

关键词: osteoclast;    osteoblast;    osteoimmunology;   

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

IL-27 regulates immune responses as well as hematopoiesis and bone remodeling, but its cellular sources in the bone remain unknown. In this study, we investigated whether osteoclasts and osteoblasts—the 2 cell types orchestrating bone homeostasis—could be a source of IL-27 and identified stimuli that induce its expression in vitro. We observed that human monocyte-derived osteoclasts expressed a broader range of TLRs than did human primary osteoblasts and that both cell types exhibited a differential induction of IL-27 expression in response to TLR or cytokine stimulation. Whereas several TLR agonists, notably TLR4 and TLR7/8 agonists, induced substantial expression of IL-27 by osteoclasts, stimulation of osteoblasts with agonists of TLR3 and/or TLR4—the 2 TLRs selectively expressed by these cells—resulted in no or low IL-27 expression. In addition, IL-27 increased TLR3 expression in osteoclasts and enhanced poly(I:C)-mediated induction of IL-27 in these cells. IFN-γ, when combined with either IL-1β plus TNF-α, IL-11, or CNTF, induced significant levels of IL-27 in osteoclasts but not in osteoblasts. In the latter cells, the addition of type I IFN, together with proinflammatory cytokines, was necessary to induce substantial levels of IL-27. Immunohistochemical studies of inflamed and remodeling bone tissue, including cases of infectious osteomyelitis and bone metastases, provided evidence that osteoclasts, osteoblasts, and occasionally osteocytes or chondrocytes, could express IL-27 in situ. This autocrine production of IL-27 by TLR- or cytokine-activated bone cells might constitute a negative-feedback mechanism to limit bone erosion and to dampen T cell–mediated immune pathology during bone inflammation.

【 授权许可】

CC BY