The mechanism of Tyk2 deficiency-induced immunosuppression in mice involves robust IL-10 production in macrophages

Hirashima, Koki; Muromoto, Ryuta; Minoguchi, Hiroya; Matsumoto, Tomohiro; Kitai, Yuichi; Kashiwakura, Jun-Ichi; Shimoda, Kazuya; Oritani, Kenji; Matsuda, Tadashi

The mechanism of Tyk2 deficiency-induced immunosuppression in mice involves robust IL-10 production in macrophages

Hirashima, Koki; Muromoto, Ryuta; Minoguchi, Hiroya et al.

Cytokine, 2020, 130, 155077

Permalink : https://hdl.handle.net/2115/82117

このアイテムのアクセス数:719件（2026-10-10 06:20 集計）

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アクセス権	open access
URI	https://hdl.handle.net/2115/82117
タイトル	The mechanism of Tyk2 deficiency-induced immunosuppression in mice involves robust IL-10 production in macrophages
著者	Hirashima, Koki ; Muromoto, Ryuta ; Minoguchi, Hiroya ; Matsumoto, Tomohiro ; Kitai, Yuichi ; Kashiwakura, Jun-Ichi ; Shimoda, Kazuya ; Oritani, Kenji ; Matsuda, Tadashi
著者名 Hirashima, Koki
e-Rad_Researcher 30455597 著者名 Muromoto, Ryuta
著者名 Minoguchi, Hiroya
著者名 Matsumoto, Tomohiro
e-Rad_Researcher 90756165 著者名 Kitai, Yuichi
e-Rad_Researcher 90373290 著者名 Kashiwakura, Jun-Ichi
著者名 Shimoda, Kazuya
著者名 Oritani, Kenji
e-Rad_Researcher 20212219 著者名 Matsuda, Tadashi
言語	英語
キーワード	Tyk2
	Macrophage plasticity
	Inflammation
	Interferon
	IL-10
発行日	2020-06
出版者	Elsevier
収録物名	Cytokine
巻(号)	130
ページ	155077
抄録	Macrophages are highly plastic in their pro-inflammatory/anti-inflammatory roles. Type I and II interferons (IFNs) are known to modulate macrophage activation. Tyrosine kinase 2 (Tyk2) has an intimate relationship with type I and II IFN signaling. Animal studies have shown that Tyk2 knock-out (KO) in mice is associated with reduced inflammatory responses in various mouse models of diseases. To investigate the role of Tyk2 in inflammation in more detail, we intraperitoneally injected heat-killed Propionibacterium acnes (P. acnes) to Tyk2 KO mice. P. acnes-induced acute peritoneal inflammation, assessed by neutrophil infiltration, was reduced in Tyk2 KO mice. The reduction was accompanied with diminished productions of inflammatory cytokines and an enhanced production of anti-inflammatory IL-10. Unexpectedly, pre-treatment of wild-type mice with the neutralizing antibodies for IFNs did not affect P. acnes-induced neutrophil infiltration. A neutralizing antibody for the IL-10 receptor in Tyk2 KO mice restored P. acnes-induced peritoneal inflammation. Enhanced production of IL-10 from Tyk2 KO peritoneal cells was suppressed by either the cyclooxygenase inhibitor diclofenac or protein kinase A inhibitor H-89. The level of prostaglandin E-2 (PGE(2)) in the steady-state peritoneal cavity in Tyk2 KO mice was higher than that in wild-type mice. Tyk2 KO macrophages showed an enhanced CREB phosphorylation induced by P. acnes plus PGE(2). Taken together, these results showed that Tyk2 deficiency potentiates the PGE(2)-protein kinase A-IL-10 pathway in macrophages, and thereby contributes to potentiation of the immunosuppressive phenotype.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	©2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	1043-4666
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.cyto.2020.155077