T-bet deficiency and Hic1 induction override TGF-β-dependency in the formation of CD103+ intestine-resident memory CD8+ T cells

Liwen Wang; Shruti Mishra; Kenneth Ka-Ho Fan; Sara Quon; Guo Li; Bingfei Yu; Wei Liao; Yong Liu; Xin Zhang; Yuanzheng Qiu; Yue Li; Ananda W. Goldrath; Chaoyu Ma; Nu Zhang

Cell Reports (Jun 2024)

T-bet deficiency and Hic1 induction override TGF-β-dependency in the formation of CD103+ intestine-resident memory CD8+ T cells

Liwen Wang,
Shruti Mishra,
Kenneth Ka-Ho Fan,
Sara Quon,
Guo Li,
Bingfei Yu,
Wei Liao,
Yong Liu,
Xin Zhang,
Yuanzheng Qiu,
Yue Li,
Ananda W. Goldrath,
Chaoyu Ma,
Nu Zhang

Affiliations

Liwen Wang: Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China
Shruti Mishra: Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
Kenneth Ka-Ho Fan: Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
Sara Quon: Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA
Guo Li: Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Clinical Research Center for Laryngopharyngeal and Voice Disorders in Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
Bingfei Yu: Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA
Wei Liao: Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
Yong Liu: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Clinical Research Center for Laryngopharyngeal and Voice Disorders in Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
Xin Zhang: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Clinical Research Center for Laryngopharyngeal and Voice Disorders in Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
Yuanzheng Qiu: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Clinical Research Center for Laryngopharyngeal and Voice Disorders in Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
Yue Li: Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
Ananda W. Goldrath: Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA
Chaoyu Ma: Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Corresponding author
Nu Zhang: Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; South Texas Veterans Health Care System, San Antonio, TX 78229, USA; Corresponding author

Journal volume & issue: Vol. 43, no. 6
p. 114258

Abstract

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Summary: Transforming growth factor β (TGF-β) represents a well-established signal required for tissue-resident memory T cell (TRM) formation at intestinal surfaces, regulating the expression of a large collection of genes coordinately promoting intestinal TRM differentiation. The functional contribution from each TGF-β-controlled transcription factor is not entirely known. Here, we find that TGF-β-induced T-bet downregulation and Hic1 induction represent two critical events during intestinal TRM differentiation. Importantly, T-bet deficiency significantly rescues intestinal TRM formation in the absence of the TGF-β receptor. Hic1 induction further strengthens TRM maturation in the absence of TGF-β and T-bet. Our results reveal that provision of certain TGF-β-induced molecular events can partially replace TGF-β signaling to promote the establishment of intestinal TRMs, which allows the functional dissection of TGF-β-induced transcriptional targets and molecular mechanisms for TRM differentiation.

CP: Immunology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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