title: IL-32γ induces chemotaxis of activated T cells via dendritic cell-derived CCL5.
abstract: Interleukin (IL)-32 has been associated with a variety of inflammatory diseases including rheumatoid arthritis, vasculitis and Crohn's disease. We have previously reported that IL-32γ, the IL-32 isoform with the highest biological activity, could act as an immune modulator through regulation of dendritic cell (DC) functions in immune responses. Cell locomotion is crucial for induction of an effective immune response. In this study, we investigated the effect and underlying mechanisms of IL-32γ on recruitment of T cells. IL-32γ upregulated the expression of several chemokines including CCL2, CCL4, and CCL5 in the DCs. In particular, IL-32γ significantly increased CCL5 expression in a dose-dependent manner. Treatment with JNK and NF-κB inhibitors suppressed IL-32γ-induced CCL5 expression in DCs, indicating that IL-32γ induced CCL5 production through the JNK and NF-κB pathways. Furthermore, supernatants from IL-32γ-treated DCs showed chemotactic activities controlling migration of activated CD4(+) and CD8(+) T cells, and these activities were suppressed by addition of neutralizing anti-CCL5 antibody. These results show that IL-32γ effectively promotes migration of activated T cells via CCL5 production in DCs. The chemotactic potential of IL-32γ may explain the pro-inflammatory effects of IL-32 and the pathologic role of IL-32 in immune disorders such as rheumatoid arthritis.
authors.affiliation: Department of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Mi Hye
authors.initials: MH
authors.lastname: Son
authors.affiliation: Department of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Jung
authors.affiliation: Department of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Seulah
authors.initials: S
authors.lastname: Choi
authors.affiliation: Department of Life Science, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Daeho
authors.initials: D
authors.lastname: Cho
authors.affiliation: Department of Life Sciences, Korea University, Seoul 136-701, Republic of Korea. Electronic address: tskim@korea.ac.kr.
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Kim
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000276:immunology*; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D007378:Interleukins / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes
chemical_list: C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D007378:Interleukins; C569037:interleukin-32, mouse
keywords: Activated T cells; CCL5; Chemotaxis; Dendritic cells; IL-32