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

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.