Batf is important for IL-4 expression in T follicular helper cells.
Apart from T helper (Th)-2 cells, T follicular helper (Tfh) cells are a major class of IL-4-producing T cells, required for regulation of type 2 humoral immunity; however, transcriptional control of IL-4 production in Tfh cells remains mainly unknown. Here, we show that the basic leucine zipper transcription factor ATF-like, Batf is important for IL-4 expression in Tfh cells rather than in canonical Th2 cells. Functionally, Batf in cooperation with interferon regulatory factor (IRF) 4 along with Stat3 and Stat6 trigger IL-4 production in Tfh cells by directly binding to and activation of the CNS2 region in the IL-4 locus. In addition, Batf-to-c-Maf signalling is an important determinant of IL-4 expression in Tfh cells. Batf deficiency impairs the generation of IL-4-producing Tfh cells that results in protection against allergic asthma. Our results thus indicate a positive role of Batf in promoting the generation of pro-allergic IL-4-producing Tfh cells.
Department of Immunology, MD Anderson Cancer Center, Houston, Texas 77030, USA.
Anupama
A
Sahoo
Department of Immunology, MD Anderson Cancer Center, Houston, Texas 77030, USA.
Andrei
A
Alekseev
1] Department of Immunology, MD Anderson Cancer Center, Houston, Texas 77030, USA [2] CNMC, Center for Cancer and Immunology Research, Children's National Medical Center, Washington, District of Columbia 20010, USA.
Kentaro
K
Tanaka
Department of Immunology, MD Anderson Cancer Center, Houston, Texas 77030, USA.
Lidiya
L
Obertas
Department of Immunology, MD Anderson Cancer Center, Houston, Texas 77030, USA.
Beatrisa
B
Lerman
Department of Melanoma Medical Oncology, MD Anderson Cancer Center, Houston, Texas 77030, USA.
Cara
C
Haymaker
Division of Cancer Medicine, Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas 77030, USA.
Karen
K
Clise-Dwyer
Division of Cancer Medicine, Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, Texas 77030, USA.
John S
JS
McMurray
Department of Immunology, MD Anderson Cancer Center, Houston, Texas 77030, USA.
Roza
R
Nurieva
D019264:Adoptive Transfer; D000818:Animals; D001249:Asthma / Q000276:immunology; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation / Q000502:physiology*; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
D050976:Basic-Leucine Zipper Transcription Factors; C431772:Batf protein, mouse; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015847:Interleukin-4; D010047:Ovalbumin