Bach2 antagonizes leukotriene B4-Ltb4r1-JunB signaling to constrain Tfh13 cell differentiation

  • Cell Rep. 2026 Apr 7;45(4):117220. doi: 10.1016/j.celrep.2026.117220.
Lin Zhu  1 ,  Heng Zhang  2 ,  Qianwen Hu  3 ,  Min Zhang  4 ,  Wenqian Zhang  5 ,  Chuanxin Huang  6
Affiliations
  • 1. Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2. Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.
  • 3. Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 4. Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5. Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: [email protected].
  • 6. Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: [email protected].
PMID: 41950005 DOI: 10.1016/j.celrep.2026.117220
Abstract

Follicular helper T (Tfh) 13 cells, a rare Tfh subpopulation co-expressing interleukin-4 (IL-4) and IL-13, are uniquely induced by type 2 allergens and essential for high-affinity IgE production. However, the regulatory circuits governing their differentiation remain elusive. Here, we report that transcriptional repressor Bach2 ablation in T cells unexpectedly promotes Tfh13 differentiation and elicits high-affinity IgE responses to type 1 immunity. Tfh13 cells exhibit a distinct transcriptional profile, marked by upregulation of leukotriene B4 (LTB4) receptor 1 (Ltb4r1). Bach2 deficiency initiates Tfh13 cell differentiation, driving an early surge of high-affinity IgE. Upon allergen rechallenge, IgE-mediated LTB4 release activates Ltb4r1 signaling to enhance JunB-dependent expression of type 2 cytokines to amplify Tfh13 polarization. Mechanistically, Bach2 directly suppresses Ltb4r1 transcription and antagonizes JunB activity by competing for the activator protein 1 (AP-1) motif at type 2 cytokine loci. Together, our findings establish Bach2 as a negative regulator of Tfh13 development by antagonizing LTB4-Ltb4r1-JunB signaling.

Keywords
Bach2; CP: Immunology; IgE; JunB; Ltb4r1; Tfh13 cells; leukotriene B4.
Products