TACI Constrains TH17 Pathogenicity and Protects against Gut Inflammation

Andy Hee-Meng Tan; Gloria Hoi Wan Tso; Biyan Zhang; Pei-Yun Teo; Xijun Ou; Sze-Wai Ng; Alex Xing Fah Wong; Sean Jing Xiang Tan; Arleen Sanny; Susana Soo-Yeon Kim; Alison P Lee; Shengli Xu; Kong-Peng Lam

doi:10.1016/j.isci.2020.101707

TACI Constrains T_H17 Pathogenicity and Protects against Gut Inflammation

iScience. 2020 Oct 22;23(11):101707. doi: 10.1016/j.isci.2020.101707. eCollection 2020 Nov 20.

Authors

Andy Hee-Meng Tan¹, Gloria Hoi Wan Tso¹, Biyan Zhang¹, Pei-Yun Teo¹, Xijun Ou¹, Sze-Wai Ng¹, Alex Xing Fah Wong¹, Sean Jing Xiang Tan¹, Arleen Sanny¹, Susana Soo-Yeon Kim¹, Alison P Lee¹, Shengli Xu^{1

2}, Kong-Peng Lam^{1

3

2

4

5

6}

Affiliations

¹ Bioprocessing Technology Institute, Agency for Science, Technology and Research, 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
² Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore.
³ Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
⁴ Departments of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore.
⁵ Departments of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore.
⁶ School of Biological Sciences, Nanyang Technological University, Singapore 639798, Singapore.

Abstract

TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) plays critical roles in B cells by promoting immunoglobulin class switching and plasma cell survival. However, its expression and function in T cells remain controversial. We show here that TACI expression can be strongly induced in murine CD4⁺ T cells in vitro by cytokines responsible for T_H17 but not T_H1 or T_H2 differentiation. Frequencies and numbers of T_H17 cells were elevated in TACI^-/ ^- compared with wild-type mice as well as among TACI^-/ ^- versus wild-type CD4⁺ T cells in mixed bone marrow chimeras, arguing for a T cell-intrinsic effect in the contribution of TACI deficiency to T_H17 cell accumulation. TACI^-/ ^- mice were more susceptible to severe colitis induced by dextran sodium sulfate or adoptive T cell transfer, suggesting that TACI negatively regulates T_H17 function and limits intestinal inflammation in a cell-autonomous manner. Finally, transcriptomic and biochemical analyses revealed that TACI^-/ ^- CD4⁺ T cells exhibited enhanced activation of T_H17-promoting transcription factors NFAT, IRF4, c-MAF, and JUNB. Taken together, these findings reveal an important role of TACI in constraining T_H17 pathogenicity and protecting against gut disease.

Keywords: Immunology.