Systemic IL-27 administration prevents abscess formation and osteolysis via local neutrophil recruitment and activation

作     者：Yugo Morita Motoo Saito Javier Rangel-Moreno Anthony M.Franchini John R.Owen John C.Martinez John L.Daiss Karen L.de Mesy Bentley Stephen L.Kates Edward M.Schwarz Gowrishankar Muthukrishnan Yugo Morita;Motoo Saito;Javier Rangel-Moreno;Anthony M.Franchini;John R.Owen;John C.Martinez;John L.Daiss;Karen L.de Mesy Bentley;Stephen L.Kates;Edward M.Schwarz;Gowrishankar Muthukrishnan

作者机构：Center for Musculoskeletal ResearchUniversity of Rochester Medical CenterRochesterNYUSA Division of AllergyImmunology and RheumatologyDepartment of MedicineUniversity of Rochester Medical CenterRochesterNYUSA Department of Environmental MedicineUniversity of Rochester School of Medicine and DentistryRochesterNYUSA Department of Orthopedic SurgeryVirginia Commonwealth UniversityRichmondVAUSA Department of OrthopedicsUniversity of Rochester Medical CenterRochesterNYUSA Department of Pathology and Laboratory MedicineUniversity of Rochester Medical CenterRochesterNYUSA 

出 版 物：《Bone Research》 (骨研究（英文版）)

年 卷 期：2022年第10卷第4期

页      面：826-837页

核心收录：

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基　　金：supported by an NIH NIAMS P30 AR069655 pilot grant (G.M.) with additional support from NIH NIAID R21 AI69736 (G.M.) NIH NIAMS P50 AR072000(E.M.S.) P30 AR069655 (E.M.S.) the AO Trauma Clinical Priority Program (E.M.S.,S.L.K.) internal funds of the Department of Medicine and R01A111914 (J.R.M.) 

主　　题：abscess protective immunity 

摘      要：Interleukin-27 is a pleiotropic cytokine whose functions during bacterial infections remain controversial,and its role in patients with *** osteomyelitis is *** address this knowledge gap,we completed a clinical study and observed elevated serum IL-27 levels(20-fold higher,P0.05)in patients compared with healthy ***,IL-27 serum levels were 60-fold higher in patients immediately following septic death than in uninfected patients(P0.05),suggesting a pathogenic role of *** test this hypothesis,we evaluated *** osteomyelitis in WT and IL-27Rα^(−/−)mice with and without exogenous IL27 induction by intramuscular injection of rAAV-IL-27p28 or rAAV-GFP,*** found that IL-27 was induced at the surgical site within 1 day of *** infection of bone and was expressed by M0,M1 and M2 macrophages and osteoblasts but not by ***,exogenous IL-27p28(~2 ng·mL^(−1) in serum)delivery ameliorated soft tissue abscesses and periimplant bone loss during infection,accompanied by enhanced local IL-27 expression,significant accumulation of RORγt^(+)neutrophils at the infection site,a decrease in RANK^(+) cells,and compromised osteoclast *** effects were not observed in IL-27Rα^(−/−)mice compared with WT mice,suggesting that IL-27 is dispensable for immunity but mediates redundant immune and bone cell functions during *** vitro studies and bulk RNA-seq of infected tibiae showed that IL-27 increased nos1,nos2,il17α,il17f,and rorc expression but did not directly stimulate ***,these results identify a novel phenomenon of IL-27 expression by osteoblasts immediately following *** infection of bone and suggest a protective role of systemic IL-27 in osteomyelitis.