OpenLB
Open Library of Bioscience
Advanced Search
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
02, 2022;22 (2): 414-426.

Genetically targeting the BATF family transcription factors BATF and BATF3 in the mouse abrogates effector T cell activities and enables long-term heart allograft survival.

Yixuan Wang, Xiang Xiao, Gangcheng Kong, Mou Wen, Guangchuan Wang, Rafik M Ghobrial, Nianguo Dong, Wenhao Chen, Xian C Li
Author Information
  1. Yixuan Wang: Immunobiology & Transplant Science Center and Department of Surgery, Houston Methodist Hospital, Houston, Texas.
  2. Xiang Xiao: Immunobiology & Transplant Science Center and Department of Surgery, Houston Methodist Hospital, Houston, Texas.
  3. Gangcheng Kong: Immunobiology & Transplant Science Center and Department of Surgery, Houston Methodist Hospital, Houston, Texas.
  4. Mou Wen: Immunobiology & Transplant Science Center and Department of Surgery, Houston Methodist Hospital, Houston, Texas.
  5. Guangchuan Wang: Immunobiology & Transplant Science Center and Department of Surgery, Houston Methodist Hospital, Houston, Texas.
  6. Rafik M Ghobrial: Immunobiology & Transplant Science Center and Department of Surgery, Houston Methodist Hospital, Houston, Texas.
  7. Nianguo Dong: Immunobiology & Transplant Science Center and Department of Surgery, Houston Methodist Hospital, Houston, Texas.
  8. Wenhao Chen: Immunobiology & Transplant Science Center and Department of Surgery, Houston Methodist Hospital, Houston, Texas. ORCID
  9. Xian C Li: Immunobiology & Transplant Science Center and Department of Surgery, Houston Methodist Hospital, Houston, Texas. ORCID
PMID: 34599765 DOI: 10.1111/ajt.16861

Abstract

T cells must be activated and become effectors first before executing allograft rejection, a process that is regulated by diverse signals and transcription factors. In this study, we studied the basic leucine zipper ATF-like transcription factor (BATF) family members in regulating T cell activities in a heart transplant model and found that mice deficient for both BATF and BATF3 (Batf Batf3 mice) spontaneously accept the heart allografts long-term without tolerizing therapies. Similarly, adoptive transfer of wild type T cells into Rag1 hosts induced prompt rejection of heart and skin allografts, whereas the Batf Batf3 T cells failed to do so. Analyses of graft-infiltrating cells showed that Batf Batf3 T cells infiltrate the graft but fail to acquire an effector phenotype (CD44 KLRG1 ). Co-transfer experiments in a T cell receptor transgenic TEa model revealed that the Batf Batf3 T cells fail to expand in vivo, retain a quiescent phenotype (CD62L CD127 ), and unable to produce effector cytokines to alloantigen stimulation, which contrasted sharply to that of wild type T cells. Together, our data demonstrate that the BATF and BATF3 are critical regulators of T effector functions, thus making them attractive targets for therapeutic interventions in transplant settings.

Keywords

T cell biology basic (laboratory) research/science immunobiology tolerance: experimental

References

J Immunol. 2000 Jul 15;165(2):860-8 [PMID: 10878360]
Immunity. 2020 Feb 18;52(2):295-312.e11 [PMID: 31924477]
Nat Immunol. 2011 Jun;12(6):536-43 [PMID: 21572431]
Cell Rep. 2018 Jul 17;24(3):607-618 [PMID: 30021159]
J Immunol. 2009 Jan 1;182(1):379-90 [PMID: 19109169]
Am J Transl Res. 2016 Aug 15;8(8):3603-13 [PMID: 27648151]
Nature. 2012 Oct 25;490(7421):543-6 [PMID: 22992523]
Immunity. 2017 Dec 19;47(6):1114-1128.e6 [PMID: 29221730]
J Vis Exp. 2018 Aug 23;(138): [PMID: 30199044]
J Exp Med. 2010 Apr 12;207(4):823-36 [PMID: 20351058]
Cytokine Growth Factor Rev. 2016 Aug;30:39-45 [PMID: 26970726]
Nature. 2012 Oct 25;490(7421):502-7 [PMID: 22992524]
Am J Transplant. 2018 Mar;18(3):604-616 [PMID: 29044999]
Oncogene. 2000 Mar 30;19(14):1752-63 [PMID: 10777209]
J Exp Med. 2020 Jan 6;217(1): [PMID: 31653690]
J Allergy Clin Immunol. 2014 Jan;133(1):198-206.e1-9 [PMID: 24290279]
Front Immunol. 2018 Nov 05;9:2548 [PMID: 30455697]
Immunity. 1997 Aug;7(2):197-208 [PMID: 9285405]
Am J Transplant. 2020 Sep;20(9):2366-2379 [PMID: 32167228]
Nature. 2009 Jul 16;460(7253):405-9 [PMID: 19578362]
Bioinformatics. 2013 Jan 1;29(1):15-21 [PMID: 23104886]
Nat Immunol. 2021 Aug;22(8):996-1007 [PMID: 34282329]
Nat Immunol. 2014 Dec;15(12):1104-15 [PMID: 25396352]
Exp Mol Med. 2019 Nov 27;51(11):1-12 [PMID: 31776325]
J Clin Invest. 2013 Nov;123(11):4641-53 [PMID: 24216482]
Nat Rev Immunol. 2013 Jul;13(7):499-509 [PMID: 23787991]
Nat Immunol. 2017 May;18(5):563-572 [PMID: 28346410]
Nat Commun. 2016 Aug 24;7:12623 [PMID: 27554168]
J Immunol. 2006 Feb 1;176(3):1394-401 [PMID: 16424166]
Am J Transplant. 2019 Mar;19(3):884-893 [PMID: 30468559]
Nat Rev Immunol. 2014 Jul;14(7):435-46 [PMID: 24962260]

Grants

  1. R01 AI129906/NIAID NIH HHS
  2. R56 AI129906/NIAID NIH HHS

MeSH Term

Allografts
Animals
Basic-Leucine Zipper Transcription Factors
Gene Expression Regulation
Interferon Regulatory Factors
Mice
Mice, Inbred C57BL
Mice, Knockout
T-Lymphocytes

Chemicals

Basic-Leucine Zipper Transcription Factors
Batf protein, mouse
Interferon Regulatory Factors
Journal Article Research Support, N.I.H., Extramural

Word Cloud

Similar Articles

Cited By