title: Activation of the interleukin-34 inflammatory pathway in response to influenza A virus infection.
abstract: Interleukin 34 (IL-34) is a newly recognized cytokine that functions similarly to macrophage colony-stimulating factor. This study investigated the mechanism by which IL-34 is produced in response to exogenous pathogen infections in humans. The results showed that the IL-34 levels were higher in the serum and peripheral blood mononuclear cells (PBMCs) from 155 influenza A virus (IAV)-infected patients than in those from 145 healthy individuals. The expression level of IL-34 in IAV-infected PBMCs was blocked by IL-22-specific siRNA. This result indicated that IL-34 was induced by IL-22 in the inflammatory cascade. The mRNA and protein expression levels of IL-22 activated by IAV infection were significantly inhibited by IL-34 overexpression but induced by IL-34-specific siRNA. Thus, a feedback system most likely exists between IL-34 and IL-22. The IL-22 expression in T helper type 17 (Th17) cells of PBMCs was higher than IL-34 expression in Th17 cells of PBMCs, and there was IL-34 expression in IL-22+ Th17 cells. This result showed that the production of IL-22 and IL-34 is both from the same and different subset of cells, which indicated that the regulatory mechanism of IL-22/IL-34 is through the autocrine or paracrine systems. In conclusion, IL-34 is induced by IL-22 in the inflammatory cascade in response to IAV infection. Therefore, IL-34 is a promising target for the screening of anti-inflammatory medicines.
authors.affiliation: Department of General Surgery (GY, YB, SZ, ZL), Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China; Department of Head and Neck Surgery (WL), Hubei Cancer Hospital, Wuhan, China; Department of Internal Medicine Oncology (LX), Huangshi Central Hospital, Huangshi, China; and Department of Orthopedic (YL), Taihe Hospital, Hubei University of Medicine, Shiyan, China.
authors.forename: Guozheng
authors.initials: G
authors.lastname: Yu
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Bing
authors.forename: Siying
authors.initials: S
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Xia
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Zhisu
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000328:Adult; D019898:Autocrine Communication / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000821:virology; D009980:Influenza A virus; D007251:Influenza, Human / Q000378:metabolism* / Q000473:pathology; D007378:Interleukins / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D019899:Paracrine Communication / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D058504:Th17 Cells / Q000378:metabolism* / Q000473:pathology; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D034741:RNA, Small Interfering; D000097043:Interleukin-22; C529076:IL34 protein, human