TNF Receptor–Associated Factor 5 Limits Function of Plasmacytoid Dendritic Cells by Controlling IFN Regulatory Factor 5 Expression | Zendy

Shuhei Kobayashi | Zendy; Tsuyoshi Sakurai | Zendy; Takanori So | Zendy; Yuka Shiota | Zendy; Atsuko Asao | Zendy; Hai The Phung | Zendy; Riou Tanaka | Zendy; Takeshi Kawabe | Zendy; Takashi Maruyama | Zendy; Emi Kanno | Zendy; Kazuyoshi Kawakami | Zendy; Yuji Owada | Zendy; Naoto Ishii | Zendy

Open Access

TNF Receptor–Associated Factor 5 Limits Function of Plasmacytoid Dendritic Cells by Controlling IFN Regulatory Factor 5 Expression

Author(s) -

Shuhei Kobayashi,

Tsuyoshi Sakurai,

Takanori So,

Yuka Shiota,

Atsuko Asao,

Hai The Phung,

Riou Tanaka,

Takeshi Kawabe,

Takashi Maruyama,

Emi Kanno,

Kazuyoshi Kawakami,

Yuji Owada,

Naoto Ishii

Publication year - 2019

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.1900188

Subject(s) - plasmacytoid dendritic cell , tumor necrosis factor alpha , microbiology and biotechnology , function (biology) , interferon regulatory factors , immunology , biology , cancer research , dendritic cell , immune system , innate immune system

The physiological functions of TNF receptor-associated factor 5 (TRAF5) in the skin inflammation and wound healing process are not well characterized. We found tha Traf5 -/- mice exhibited an accelerated skin wound healing as compared with wild-type counterparts. The augmented wound closure in Traf5 -/- mice was associated with a massive accumulation of plasmacytoid dendritic cells (pDCs) into skin wounds and an enhanced expression of genes related to wound repair at skin sites. In accordance with this result, adoptive transfer of Traf5 -/- pDCs, but not wild-type pDCs, into the injured skin area in wild-type recipient mice significantly promoted skin wound healing. The expression of skin-tropic chemokine receptor CXCR3 was significantly upregulated in Traf 5 -/- pDCs, and treatment with a CXCR3 inhibitor cancelled the promoted wound healing in Traf 5 -/- mice, suggesting a pivotal role of CXCR3 in pDC-dependent wound healing. Traf5 -/- pDCs displayed significantly higher expression of IFN regulatory factor 5 (IRF5), which correlated with greater induction of proinflammatory cytokine genes and CXCR3 protein after stimulation with TLR ligands. Consistently, transduction of exogeneous TRAF5 in Traf 5 -/- pDCs normalized the levels of abnormally elevated proinflammatory molecules, including IRF5 and CXCR3. Furthermore, knockdown of IRF5 also rescued the abnormal phenotypes of Traf 5 -/- pDCs. Therefore, the higher expression and induction of IRF5 in Traf 5 -/- pDCs causes proinflammatory and skin-tropic characteristics of the pDCs, which may accelerate skin wound healing responses. Collectively, our results uncover a novel role of TRAF5 in skin wound healing that is mediated by IRF5-dependent function of pDCs.

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