title: The involvement of endoplasmic reticulum stress response in immune dysfunction of dendritic cells after severe thermal injury in mice.
abstract: Suppressed adaptive immune function is one of the major concerns responsible for the development of opportunistic infections and subsequent sepsis with high mortality in severe burns. Endoplasmic reticulum stress (ERS) is the endogenous self-protective mechanism, and it plays an important role in almost every process of living by regulating the balance between homeostasis and apoptosis. The current study investigated the involvement of ERS in the pathogenesis of dysfunction of dendritic cells (DCs) in burn mice. Our results show a significant ERS response in splenic DC after burn injury. Treatment with salubrinal (Sal, reported to protect cells against ERS-induced apoptosis.) decrease the apoptotic rate of DC induced by burns, and promote maturation and activation of DC, as well as the ability to promote T cell proliferation and polarization towards Th1 immunity (all P<0.05). Gene silence of XBP-1 (key molecular in ERS response) results in the increased apoptosis and suppressed phenotypical maturation of splenic DC in burn mice. These results show that the excessive ERS is essential for immunosuppression during severe thermal injury. XBP-1 plays a pivotal role in DC functional immunomodulation in burn mice. Inhibition of apoptotic ERS response benefits mice from major burns.
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing, China.|Department of Microbiology and Immunology, Trauma Research Center, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, China.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Zhu
authors.affiliation: Department of Microbiology and Immunology, Trauma Research Center, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Dong
authors.affiliation: Department of Microbiology and Immunology, Trauma Research Center, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, China.
authors.forename: Yan-Bo
authors.initials: YB
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, Trauma Research Center, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, China.
authors.forename: Qing-Hong
authors.initials: QH
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Immunology, Trauma Research Center, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Microbiology and Immunology, Trauma Research Center, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, China.
authors.forename: Yong-Ming
authors.initials: YM
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Hua-Ping
authors.initials: HP
authors.lastname: Liang
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D017209:Apoptosis; D002056:Burns / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002934:Cinnamates / Q000494:pharmacology; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D008213:Lymphocyte Activation; D008297:Male; D008807:Mice, Inbred BALB C; D010641:Phenotype; D034622:RNA Interference; D012720:Severity of Illness Index; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D000071717:X-Box Binding Protein 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D002934:Cinnamates; D016207:Cytokines; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; C496827:salubrinal; D013890:Thiourea
keywords: Pathology Section; burns; dendritic cell; endoplasmic reticulum stress; immune dysfunction; sepsis