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

doi:10.1016/j.celrep.2024.114258

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

Cell Rep. 2024 Jun 25;43(6):114258. doi: 10.1016/j.celrep.2024.114258. Epub 2024 May 22.

Authors

Liwen Wang¹, Shruti Mishra², Kenneth Ka-Ho Fan², Sara Quon³, Guo Li⁴, Bingfei Yu³, Wei Liao⁵, Yong Liu⁶, Xin Zhang⁶, Yuanzheng Qiu⁶, Yue Li², Ananda W Goldrath³, Chaoyu Ma⁷, Nu Zhang⁸

Affiliations

¹ 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.
² 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.
³ Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
⁴ 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.
⁵ 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.
⁶ 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.
⁷ 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. Electronic address: [email protected].
⁸ 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. Electronic address: [email protected].

Abstract

Transforming growth factor β (TGF-β) represents a well-established signal required for tissue-resident memory T cell (T_RM) formation at intestinal surfaces, regulating the expression of a large collection of genes coordinately promoting intestinal T_RM 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 T_RM differentiation. Importantly, T-bet deficiency significantly rescues intestinal T_RM formation in the absence of the TGF-β receptor. Hic1 induction further strengthens T_RM 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 T_RMs, which allows the functional dissection of TGF-β-induced transcriptional targets and molecular mechanisms for T_RM differentiation.

Keywords: CP: Immunology.

Published by Elsevier Inc.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, CD / metabolism
CD8-Positive T-Lymphocytes* / immunology
CD8-Positive T-Lymphocytes* / metabolism
Cell Differentiation
Immunologic Memory
Integrin alpha Chains / metabolism
Intestinal Mucosa* / cytology
Intestinal Mucosa* / immunology
Intestinal Mucosa* / metabolism
Intestines / immunology
Kruppel-Like Transcription Factors* / metabolism
Memory T Cells / immunology
Memory T Cells / metabolism
Mice
Mice, Inbred C57BL
Signal Transduction*
T-Box Domain Proteins* / genetics
T-Box Domain Proteins* / metabolism
T-bet Transcription Factor
Transforming Growth Factor beta / metabolism

Substances

alpha E integrins
Antigens, CD
Hic1 protein, mouse
Integrin alpha Chains
Kruppel-Like Transcription Factors
T-Box Domain Proteins
T-bet Transcription Factor
Transforming Growth Factor beta

Abstract

Publication types

MeSH terms

Substances

Grants and funding