title: IL-37b suppresses T cell priming by modulating dendritic cell maturation and cytokine production via dampening ERK/NF-κB/S6K signalings.
abstract: Interleukin 37b (IL-37b) plays a key role in suppressing immune responses, partially by modulating the function of dendritic cells (DCs). However, the precise mechanisms are still largely unknown. Here, we investigated the effects of IL-37b on DC maturation and T cell responses induced by DCs, and explored the involved signaling pathways. It was found that IL-37b down-regulated the expressions of co-stimulatory molecules CD80 and CD86 on DCs in vitro. At the same time, the expressions of pro-inflammatory cytokines, such as TNF-α and IL-6, were suppressed, while the expression of the T cell inhibitory cytokine TGF-β was increased in IL-37b-treated DCs. In addition, the activation effect of DCs on T cells was impaired by IL-37b. We further revealed that extracellular single-regulated kinase (ERK), nuclear factor-κB (NF-κB), and mTOR-S6K signaling pathways were involved in the inhibition of DCs induced by IL-37b. This was confirmed by the similarly suppressive effect of chemical inhibitors against NF-κB, ERK, and S6K on the expressions of IL-6 and TNF-α in DCs. In conclusion, these results demonstrated that IL-37b suppressed DC maturation and immunostimulatory capacity in T cell priming by involving in ERK, NF-κB, and S6K-based inhibitory signaling pathways.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China Tianjin Dongli Hospital, Tianjin 300300, China.
authors.forename: Wantong
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Wang
authors.affiliation: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Zhonglong
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Chunmin
authors.initials: C
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Zhina
authors.initials: Z
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Han
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Song
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Zhongchao
authors.initials: Z
authors.lastname: Han
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China.
authors.forename: Hanzhi
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China xfeng1979@hotmail.com ycluo2013@163.com.
authors.forename: Yuechen
authors.initials: Y
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, Tianjin 300020, China xfeng1979@hotmail.com ycluo2013@163.com.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Feng
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D045142:Cross-Priming; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000276:immunology / Q000378:metabolism; D013491:Suppressor Factors, Immunologic / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines; D007378:Interleukins; D016328:NF-kappa B; D011994:Recombinant Proteins; D013491:Suppressor Factors, Immunologic; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C448959:ribosomal protein S6 kinase, 70kD, polypeptide 2
keywords: IL-37b; cytokines; dendritic cells