title: BATF is required for normal expression of gut-homing receptors by T helper cells in response to retinoic acid.
abstract: CCR9 and α4β7 are the major trafficking receptors for lymphocyte migration to the gut, and their expression is induced during lymphocyte activation under the influence of retinoic acid (RA). We report here that BATF (basic leucine zipper transcription factor, ATF-like), an AP-1 protein family factor, is required for optimal expression of CCR9 and α4β7 by T helper cells. BATF-deficient (knockout [KO]) mice had reduced numbers of effector T and regulatory T cells in the intestine. The intestinal T cells in BATF KO mice expressed CCR9 and α4β7 at abnormally low levels compared with their wild-type (WT) counterparts, and BATF KO CD4(+) T cells failed to up-regulate the expression of CCR9 and α4β7 to WT levels in response to RA. Defective binding of RARα and histone acetylation at the regulatory regions of the CCR9 and Itg-α4 genes were observed in BATF KO T cells. As a result, BATF KO effector and FoxP3(+) T cells failed to populate the intestine, and neither population functioned normally in the induction and regulation of colitis. Our results establish BATF as a cellular factor required for normal expression of CCR9 and α4β7 and for the homeostasis and effector functions of T cell populations in the intestine.
authors: Laboratory of Immunology and Hematopoiesis, Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA.
authors: Chuanwu
authors: C
authors: Wang
authors: Shankar
authors: S
authors: Thangamani
authors: Myunghoo
authors: M
authors: Kim
authors: Bon-Hee
authors: BH
authors: Gu
authors: Jee H
authors: JH
authors: Lee
authors: Elizabeth J
authors: EJ
authors: Taparowsky
authors: Chang H
authors: CH
authors: Kim
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000032:analysis; D007108:Immune Tolerance; D016023:Integrins / Q000032:analysis / Q000235:genetics; D007422:Intestines / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054388:Receptors, CCR / Q000032:analysis / Q000235:genetics; D016201:Receptors, Lymphocyte Homing / Q000032:analysis*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C431772:Batf protein, mouse; C119309:CC chemokine receptor 9; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016023:Integrins; C000607072:Rara protein, mouse; D054388:Receptors, CCR; D016201:Receptors, Lymphocyte Homing; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; C071777:integrin alpha4beta7; D014212:Tretinoin