Frontline Science: Human bone cells as a source of IL-27 under inflammatory conditions: role of TLRs and cytokines.
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.
INSERM U1151 CNRS UMR 8253, Université Paris Descartes, Paris, France.|Service de Pathologie, AP-HP and Université Paris Descartes, Hôpital Cochin, Paris, France; and.
Frédérique
F
Larousserie
INSERM U1151 CNRS UMR 8253, Université Paris Descartes, Paris, France.
Laura
L
Bsiri
Service de Chirurgie Orthopédique, AP-HP, Hôpital Cochin, Paris, France.
Valérie
V
Dumaine
INSERM U1151 CNRS UMR 8253, Université Paris Descartes, Paris, France.
Céline
C
Dietrich
Service de Pathologie, AP-HP and Université Paris Descartes, Hôpital Cochin, Paris, France; and.
Anne
A
Audebourg
Service de Pathologie, AP-HP and Université Paris Descartes, Hôpital Cochin, Paris, France; and.
Brigitte
B
Radenen-Bussière
Service de Chirurgie Orthopédique, AP-HP, Hôpital Cochin, Paris, France.
Philippe
P
Anract
Service de Pathologie, AP-HP and Université Paris Descartes, Hôpital Cochin, Paris, France; and.
Marie-Cécile
MC
Vacher-Lavenu
INSERM U1151 CNRS UMR 8253, Université Paris Descartes, Paris, France; odile.devergne@inserm.fr.
Odile
O
Devergne
D001859:Bone Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007378:Interleukins / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D012516:Osteosarcoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051193:Toll-Like Receptors / Q000378:metabolism*
D016207:Cytokines; D007378:Interleukins; C464565:MYDGF protein, human; D051193:Toll-Like Receptors
osteoblast; osteoclast; osteoimmunology