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Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C.
Zhao, Ming; Ren, Kaiqun; Xiong, Xiwen; Xin, Yue; Zou, Yujie; Maynard, Jason C; Kim, Angela; Battist, Alexander P; Koneripalli, Navya; Wang, Yusu; Chen, Qianyue; Xin, Ruyue; Yang, Chenyan; Huang, Rong; Yu, Jiahui; Huang, Zan; Zhang, Zengdi; Wang, Haiguang; Wang, Daoyuan; Xiao, Yihui; Salgado, Oscar C; Jarjour, Nicholas N; Hogquist, Kristin A; Revelo, Xavier S; Burlingame, Alma L; Gao, Xiang; von Moltke, Jakob; Lin, Zhaoyu; Ruan, Hai-Bin.
Afiliação
  • Zhao M; Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
  • Ren K; Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA; College of Medicine, Hunan Normal University, Changsha, Hunan, China.
  • Xiong X; School of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan, China.
  • Xin Y; School of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan, China.
  • Zou Y; MOE Key Laboratory of Model Animals for Disease Study, State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
  • Maynard JC; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.
  • Kim A; Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
  • Battist AP; Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
  • Koneripalli N; Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
  • Wang Y; MOE Key Laboratory of Model Animals for Disease Study, State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
  • Chen Q; MOE Key Laboratory of Model Animals for Disease Study, State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
  • Xin R; MOE Key Laboratory of Model Animals for Disease Study, State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
  • Yang C; School of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan, China.
  • Huang R; School of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan, China.
  • Yu J; School of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan, China.
  • Huang Z; Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
  • Zhang Z; Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
  • Wang H; Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
  • Wang D; College of Medicine, Hunan Normal University, Changsha, Hunan, China.
  • Xiao Y; College of Medicine, Hunan Normal University, Changsha, Hunan, China.
  • Salgado OC; Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
  • Jarjour NN; Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
  • Hogquist KA; Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
  • Revelo XS; Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA; Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
  • Burlingame AL; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.
  • Gao X; MOE Key Laboratory of Model Animals for Disease Study, State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
  • von Moltke J; Department of Immunology, University of Washington School of Medicine, Seattle, Washington, USA.
  • Lin Z; MOE Key Laboratory of Model Animals for Disease Study, State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China. Electronic address: linzy
  • Ruan HB; Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA; Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA. Electronic address: hruan@umn.edu.
Immunity ; 55(4): 623-638.e5, 2022 04 12.
Article em En | MEDLINE | ID: mdl-35385697
ABSTRACT
The epithelium is an integral component of mucosal barrier and host immunity. Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. However, it is unknown how helminth infection and the resulting cytokine milieu drive epithelial remodeling and orchestrate alarmin secretion. Here, we report that epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification was induced upon helminth infections. By modifying and activating the transcription factor STAT6, O-GlcNAc transferase promoted the transcription of lineage-defining Pou2f3 in tuft cell differentiation and IL-25 production. Meanwhile, STAT6 O-GlcNAcylation activated the expression of Gsdmc family genes. The membrane pore formed by GSDMC facilitated the unconventional secretion of IL-33. GSDMC-mediated IL-33 secretion was indispensable for effective anti-helminth immunity and contributed to induced intestinal inflammation. Protein O-GlcNAcylation can be harnessed for future treatment of type 2 inflammation-associated human diseases.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Alarminas / Mucosa Intestinal Limite: Humans Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Alarminas / Mucosa Intestinal Limite: Humans Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos