Stromal Interaction Molecule Deficiency in T Cells Promotes Spontaneous Follicular Helper T Cell Development and Causes Type 2 Immune Disorders
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- Masatsugu Oh-hora
- Division of Molecular Immunology, Research Center for Infectious Diseases, Medical Institute of Bioregulation, Kyushu University , Fukuoka 812-8582 ,
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- Xiuyuan Lu
- Division of Molecular and Cellular Immunology, Research Center for Infectious Diseases, Medical Institute of Bioregulation, Kyushu University , Fukuoka 812-8582 ,
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- Moe Shiokawa
- Division of Molecular and Cellular Immunology, Research Center for Infectious Diseases, Medical Institute of Bioregulation, Kyushu University , Fukuoka 812-8582 ,
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- Hiroshi Takayanagi
- Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo , Tokyo 113-0033 ,
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- Sho Yamasaki
- Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University , Suita 565-0871 ,
書誌事項
- 公開日
- 2019-05-01
- 資源種別
- journal article
- 権利情報
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- https://academic.oup.com/pages/standard-publication-reuse-rights
- DOI
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- 10.4049/jimmunol.1700610
- 公開者
- Oxford University Press (OUP)
この論文をさがす
説明
<jats:title>Abstract</jats:title> <jats:p>Appropriate T cell responses are controlled by strict balance between activatory and inhibitory pathways downstream of TCR. Although mice or humans with impaired TCR signaling develop autoimmunity, the precise molecular mechanisms linking reduced TCR signaling to autoimmunity are not fully understood. Engagement of TCR activates Ca2+ signaling mainly through store-operated Ca2+ entry activated by stromal interaction molecule (Stim) 1 and Stim2. Despite defective T cell activation, mice deficient in both Stim1 and Stim2 in T cells (conditional double knockout [cDKO]) developed lymphoproliferative disorders and skin inflammation with a concomitant increase in serum IgG1 and IgE levels. In cDKO mice, follicular helper T (Tfh) cells were dramatically increased in number, and they produced IL-4 spontaneously. These inflammatory symptoms were abolished by the deletion of IL-4 in cDKO mice. Tfh development and inflammatory symptoms in cDKO mice were abrogated by further deletion of NFAT2 in T cells. These findings suggest that Tfh cells spontaneously developed in the absence of Ca2+ signaling and caused unregulated type 2 responses.</jats:p>
収録刊行物
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- The Journal of Immunology
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The Journal of Immunology 202 (9), 2616-2627, 2019-05-01
Oxford University Press (OUP)
