Bone loss is a common feature of several autoimmune diseases and the risk of osteoporosis is increased in patients with rheumatoid arthritis (RA), inflammatory bowel disease and systemic lupus erythematosus. Hyperactivation of osteoclasts (OCs) can be a feature of certain autoimmune diseases, cancers, and infections. B7h is the ligand of the ICOS T cell costimulatory molecule, and it is expressed in haematopoietic e non-haematopoietic cells. Recent reports showed that the B7h:ICOS interaction may trigger bidirectional signals which are able to modulate the response of both the cells expressing ICOS and those expressing B7h. This work stems from our finding that OCs (differentiated in vitro from monocytes) can express B7h, and it was aimed to investigate the effect of B7h triggering on differentiation and function of OCs in vitro and in vivo. The in vitro results showed that B7h triggering using ICOS-Fc (a recombinant soluble form of ICOS) reversibly inhibited OCs differentiation evaluated in terms of morphology and CD14-Cathepsin K+TRAP+ phenotype. Moreover, it induced reduction of cell size and nuclei, decreased ability to adhere to the substrate and to promote calcium release. A similar effect was detected on already differentiated OCs. The in vivo results showed that the treatment with ICOS-Fc strikingly inhibited the systemic bone resorption induced in mice by treatment with high doses of soluble RANKL, a mouse model of osteoporosis. These results detected a novel molecular system involved in osteoimmunology and open a novel field in the pharmacological use of agonists and antagonists of the ICOS/B7h system.

B7H TRIGGERING INHIBITS OSTEOCLAST FUNCTION IN VITRO AND IN VIVO.

DIANZANI, Chiara;
2016

Abstract

Bone loss is a common feature of several autoimmune diseases and the risk of osteoporosis is increased in patients with rheumatoid arthritis (RA), inflammatory bowel disease and systemic lupus erythematosus. Hyperactivation of osteoclasts (OCs) can be a feature of certain autoimmune diseases, cancers, and infections. B7h is the ligand of the ICOS T cell costimulatory molecule, and it is expressed in haematopoietic e non-haematopoietic cells. Recent reports showed that the B7h:ICOS interaction may trigger bidirectional signals which are able to modulate the response of both the cells expressing ICOS and those expressing B7h. This work stems from our finding that OCs (differentiated in vitro from monocytes) can express B7h, and it was aimed to investigate the effect of B7h triggering on differentiation and function of OCs in vitro and in vivo. The in vitro results showed that B7h triggering using ICOS-Fc (a recombinant soluble form of ICOS) reversibly inhibited OCs differentiation evaluated in terms of morphology and CD14-Cathepsin K+TRAP+ phenotype. Moreover, it induced reduction of cell size and nuclei, decreased ability to adhere to the substrate and to promote calcium release. A similar effect was detected on already differentiated OCs. The in vivo results showed that the treatment with ICOS-Fc strikingly inhibited the systemic bone resorption induced in mice by treatment with high doses of soluble RANKL, a mouse model of osteoporosis. These results detected a novel molecular system involved in osteoimmunology and open a novel field in the pharmacological use of agonists and antagonists of the ICOS/B7h system.
Autoimmunity 2016
LIPSIA
2016
-
-
-
-
Gigliotti, Casimiro Luca; Boggio, Elena; Clemente, Nausicaa; Toth, Erika; Chiocchetti, Annalisa; Dianzani, Chiara; Bosetti, Michela; Dianzani, Umberto
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1577931
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact