BATF3 is sufficient for the induction of Il9 expression and can compensate for BATF during Th9 cell differentiation

Autor: Jung In Heo, Sung Woong Jang, Hyeong Su Kim, Gap Ryol Lee, Ga Eul Kim, So Hee Kim, Woo Ho Lee
Rok vydání: 2019
Předmět:
CD4-Positive T-Lymphocytes
0301 basic medicine
Chromatin Immunoprecipitation
Cellular differentiation
Immunoblotting
Clinical Biochemistry
lcsh:Medicine
Enzyme-Linked Immunosorbent Assay
Biology
Biochemistry
Article
lcsh:Biochemistry
Mice
03 medical and health sciences
0302 clinical medicine
Proto-Oncogene Proteins
BATF
Homologous chromosome
Animals
lcsh:QD415-436
Lung
Molecular Biology
Transcription factor
CD4-positive T cells
Mice
Knockout
Reporter gene
Reverse Transcriptase Polymerase Chain Reaction
lcsh:R
Interleukin-9
Lymphocyte differentiation
Cell Differentiation
Cell biology
Mice
Inbred C57BL
Repressor Proteins
Basic-Leucine Zipper Transcription Factors
030104 developmental biology
Interferon Regulatory Factors
Trans-Activators
Molecular Medicine
Chromatin immunoprecipitation
030215 immunology
IRF4
Zdroj: Experimental & Molecular Medicine
Experimental and Molecular Medicine, Vol 51, Iss 11, Pp 1-12 (2019)
ISSN: 2092-6413
1226-3613
DOI: 10.1038/s12276-019-0348-6
Popis: 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.
Immunology: fanning the fires of airway inflammation A protein that regulates gene expression in immune cells may contribute to airway inflammation in asthma and allergies. A subset of immune cells known as Th9 cells plays a prominent role in these respiratory disorders, and researchers led by Gap Ryol Lee at Sogang University in Seoul, South Korea, set out to characterize signaling mechanisms that promote Th9 production. They focused specifically on a protein called BATF3, which regulates genes responsible for maturation of a variety of other immune cell types, but whose role with regard to Th9 is poorly understood. They determined that BATF3 has a potent effect in terms of inducing Th9 cell activity, and can even take the place of another known Th9-inducing protein. These findings could assist in the development of treatments that keep airway-constricting inflammation in check.
Databáze: OpenAIRE
Externí odkaz: