Abstract
Th9 cells preferentially produce IL-9 and participate in allergic responses and asthma. Differentiation of Th9 cells is induced by IL-4 and TGF-β, and then the cells are amplified by OX40 signals. The transcription factors PU.1, IRF4, and BATF are required for Th9 differentiation. BATF3 is an AP-1 family transcription factor that is highly homologous to BATF; however, its role in Th9 cells is poorly defined. Here, we show that OX40 signaling induced the expression of Batf3 and that its overexpression in the presence or absence of OX40 signaling increased the expression of IL-9 in Th9 cells. BATF3 physically interacted with IRF4 and was bound to the Il9 locus. A transient reporter assay revealed that the BATF3–IRF4 complex induced Il9 promoter activity. BATF3 rescued Il9 expression and restored the capacity to induce the airway inflammation in Batf KO Th9 cells. Thus, BATF3 itself is sufficient for the induction of Th9 cell differentiation and can substitute for BATF during Th9 cell differentiation.
Highlights
CD4+ T cells are essential for coordinating immune responses
When naive CD4+ T cells were differentiated into Th9 cells in the presence of OX40 ligand (OX40L), the expression of Batf[3] and IL-9 increased markedly (Fig. 1b, c); this result is consistent with observations from previous studies[24,25]
A recent study showed that BATF3 plays a role in Treg cells[18]; OX40L signaling increases IL-9 expression in Th9 cells[23]
Summary
CD4+ T cells are essential for coordinating immune responses. These cells are comprised of several subsets, which are categorized as conventional T (Tconv) cells and regulatory T (Treg) cells. Tconv cells, comprising T helper type 1 (Th1), Th2, Th9, Th17, and T follicular helper cells, activate immune responses[1]. The balance between Tconv cells and Treg cells is important for maintaining immune homeostasis[2,3]. Recent studies show that Th9 cells are a subset of CD4+ T cells that mainly secrete interleukin (IL)-94,5. Th9 cells play an important role in allergic inflammation, autoimmune disease, and tumor immunity[6,8,9,10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
