TY - JOUR
T1 - TGF-β and Eomes control the homeostasis of CD8+regulatory T cells
AU - Mishra, Shruti
AU - Liao, Wei
AU - Liu, Yong
AU - Yang, Ming
AU - Ma, Chaoyu
AU - Wu, Haijing
AU - Zhao, Ming
AU - Zhang, Xin
AU - Qiu, Yuanzheng
AU - Lu, Qianjin
AU - Zhang, Nu
N1 - Funding Information:
Clinic and Laboratory Integration Program, and American Cancer Society grant RSG-18-222-01-LIB to N. Zhang; and National Natural Science Foundation of China grants 81522038, 81270024, and 81220108017 to Q. Lu. Flow cytometry data were generated in the University of Texas Health Science Center at San Antonio Flow Cytometry Shared Resource Facility, which is supported in part by the University of Texas Health Science Center at San Antonio, the Mays Cancer Center P30 Cancer Center Support Grant (NIH-NCI P30 CA054174), and the National Institutes of Health National Center for Advancing Translational Sciences Clinical Translational Science Award (NIH-NCATS UL1 TR002645). RNA-seq analysis of WT and Tgfbr2−/−Eomes−/− CD8+ T reg cells was performed by the Genome Sequencing Core Facility at University of Texas Health Science Center at San Antonio, which is supported by National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA054174, National Institutes of Health Shared Instrument grant 1S10OD021805-01, and Cancer Prevention and Research Institute of Texas Core Facility grant RP160732.
Funding Information:
This work is supported by National Institutes of Health grants AI125701 and AI139721, the Cancer Research Institute
Funding Information:
We thank Dr. Di Yu (Australian National University) and Dr. Stephen Jameson (University of Minnesota) for critical reading of the manuscript. We thank Dr. Ben Daniel, Karla Gorena, and SebastianMontagnino for FACS sorting. We thank Drs. Zhao Lai, Yi Zou, and Yidong Chen for RNA-seq analysis and informatics assistance. This work is supported by National Institutes of Health grants AI125701 and AI139721, the Cancer Research Institute Clinic and Laboratory Integration Program, and American Cancer Society grant RSG-18-222-01-LIB to N. Zhang; and National Natural Science Foundation of China grants 81522038, 81270024, and 81220108017 to Q. Lu. Flow cytometry data were generated in the University of Texas Health Science Center at San Antonio Flow Cytometry Shared Resource Facility, which is supported in part by the University of Texas Health Science Center at San Antonio, the Mays Cancer Center P30 Cancer Center Support Grant (NIH-NCI P30 CA054174), and the National Institutes of Health National Center for Advancing Translational Sciences Clinical Translational Science Award (NIH-NCATS UL1 TR002645). RNA-seq analysis of WT and Tgfbr2-/-Eomes-/-CD8+T reg cells was performed by the Genome Sequencing Core Facility at University of Texas Health Science Center at San Antonio, which is supported by National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA054174, National Institutes of Health Shared Instrument grant 1S10OD021805-01, and Cancer Prevention and Research Institute of Texas Core Facility grant RP160732. Author contributions: N. Zhang and S. Mishra designed mouse experiments. S. Mishra, W. Liao, Y. Liu, and C. Ma performed mouse experiments. Q. Lu, H. Wu,M. Zhao, W. Liao, and M. Yang designed and performed human experiments. S. Mishra, W. Liao, H.Wu, Q. Lu, and N. Zhang analyzed the results. X. Zhang and Y. Qiu contributed to overall experimental design and analysis. S. Mishra, Q. Lu, and N. Zhang wrote the manuscript.
Publisher Copyright:
© 2020 Mishra et al.
PY - 2021/1/4
Y1 - 2021/1/4
N2 - In addition to Foxp3+ CD4+ regulatory T cells (CD4+ T reg cells), Foxp3- CD8+ regulatory T cells (CD8+ T reg cells) are critical to maintain immune tolerance. However, the molecular programs that specifically control CD8+ but not CD4+ T reg cells are largely unknown. Here, we demonstrate that simultaneous disruption of both TGF-β receptor and transcription factor Eomesodermin (Eomes) in T cells results in lethal autoimmunity due to a specific defect in CD8+ but not CD4+ T reg cells. Further, TGF-β signal maintains the regulatory identity, while Eomes controls the follicular location of CD8+ T reg cells. Both TGF-β signal and Eomes coordinate to promote the homeostasis of CD8+ T reg cells. Together, we have identified a unique molecular program designed for CD8+ T reg cells.
AB - In addition to Foxp3+ CD4+ regulatory T cells (CD4+ T reg cells), Foxp3- CD8+ regulatory T cells (CD8+ T reg cells) are critical to maintain immune tolerance. However, the molecular programs that specifically control CD8+ but not CD4+ T reg cells are largely unknown. Here, we demonstrate that simultaneous disruption of both TGF-β receptor and transcription factor Eomesodermin (Eomes) in T cells results in lethal autoimmunity due to a specific defect in CD8+ but not CD4+ T reg cells. Further, TGF-β signal maintains the regulatory identity, while Eomes controls the follicular location of CD8+ T reg cells. Both TGF-β signal and Eomes coordinate to promote the homeostasis of CD8+ T reg cells. Together, we have identified a unique molecular program designed for CD8+ T reg cells.
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U2 - 10.1084/JEM.20200030
DO - 10.1084/JEM.20200030
M3 - Article
C2 - 32991667
AN - SCOPUS:85092446737
SN - 0022-1007
VL - 218
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 1
M1 - e20200030
ER -