Allergic TH2 Response Governed by B-Cell Lymphoma 6 Function in Naturally Occurring Memory Phenotype CD4+ T Cells
Transcriptional repressor B-cell lymphoma 6 (Bcl6) appears to regulate TH2 immune responses in allergies, but its precise role is unclear. We previously reported that Bcl6 suppressed IL-4 production in naïve CD4+ T cell-derived memory TH2 cells. To investigate Bcl6 function in allergic responses in...
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doaj-d2fd1e26406c41e19cd9be331a9172e42020-11-24T22:34:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-04-01910.3389/fimmu.2018.00750328510Allergic TH2 Response Governed by B-Cell Lymphoma 6 Function in Naturally Occurring Memory Phenotype CD4+ T CellsTakashi Ogasawara0Yuko Kohashi1Jun Ikari2Toshibumi Taniguchi3Nobuhide Tsuruoka4Haruko Watanabe-Takano5Lisa Fujimura6Akemi Sakamoto7Masahiko Hatano8Hirokuni Hirata9Yasutsugu Fukushima10Takeshi Fukuda11Kazuhiro Kurasawa12Koichiro Tatsumi13Takeshi Tokuhisa14Masafumi Arima15Masafumi Arima16Department of Respirology (B2), Chiba University Graduate School of Medicine, Chiba, JapanDepartment of Biomedical Science (M14), Chiba University Graduate School of Medicine, Chiba, JapanDepartment of Respirology (B2), Chiba University Graduate School of Medicine, Chiba, JapanDepartment of Biomedical Science (M14), Chiba University Graduate School of Medicine, Chiba, JapanDepartment of Reproductive Medicine (G4), Chiba University Graduate School of Medicine, Chiba, JapanDepartment of Biomedical Science (M14), Chiba University Graduate School of Medicine, Chiba, JapanBiomedical Research Center, Chiba University, Chiba, JapanDepartment of Biomedical Science (M14), Chiba University Graduate School of Medicine, Chiba, JapanDepartment of Biomedical Science (M14), Chiba University Graduate School of Medicine, Chiba, JapanDepartment of Respiratory Medicine and Clinical Immunology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, JapanDepartment of Respiratory Medicine and Clinical Immunology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, JapanDepartment of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, Mibu, JapanDepartment of Rheumatology, Dokkyo Medical University School of Medicine, Mibu, JapanDepartment of Respirology (B2), Chiba University Graduate School of Medicine, Chiba, JapanDepartment of Developmental Genetics, Chiba University Graduate School of Medicine, Chiba, JapanDepartment of Biomedical Science (M14), Chiba University Graduate School of Medicine, Chiba, JapanDepartment of Rheumatology, Dokkyo Medical University School of Medicine, Mibu, JapanTranscriptional repressor B-cell lymphoma 6 (Bcl6) appears to regulate TH2 immune responses in allergies, but its precise role is unclear. We previously reported that Bcl6 suppressed IL-4 production in naïve CD4+ T cell-derived memory TH2 cells. To investigate Bcl6 function in allergic responses in naturally occurring memory phenotype CD4+ T (MPT) cells and their derived TH2 (MPTH2) cells, Bcl6-manipulated mice, highly conserved intron enhancer (hcIE)-deficient mice, and reporter mice for conserved noncoding sequence 2 (CNS2) 3′ distal enhancer region were used to elucidate Bcl6 function in MPT cells. The molecular mechanisms of Bcl6-mediated TH2 cytokine gene regulation were elucidated using cellular and molecular approaches. Bcl6 function in MPT cells was determined using adoptive transfer to naïve mice, which were assessed for allergic airway inflammation. Bcl6 suppressed IL-4 production in MPT and MPTH2 cells by suppressing CNS2 enhancer activity. Bcl6 downregulated Il4 expression in MPTH2 cells, but not MPT cells, by suppressing hcIE activity. The inhibitory functions of Bcl6 in MPT and MPTH2 cells attenuated allergic responses. Bcl6 is a critical regulator of IL-4 production by MPT and MPTH2 cells in TH2 immune responses related to the pathogenesis of allergies.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00750/fullB-cell lymphoma 6naturally occurring memory phenotype T cellsallergyTH2 cellsasthma |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Takashi Ogasawara Yuko Kohashi Jun Ikari Toshibumi Taniguchi Nobuhide Tsuruoka Haruko Watanabe-Takano Lisa Fujimura Akemi Sakamoto Masahiko Hatano Hirokuni Hirata Yasutsugu Fukushima Takeshi Fukuda Kazuhiro Kurasawa Koichiro Tatsumi Takeshi Tokuhisa Masafumi Arima Masafumi Arima |
spellingShingle |
Takashi Ogasawara Yuko Kohashi Jun Ikari Toshibumi Taniguchi Nobuhide Tsuruoka Haruko Watanabe-Takano Lisa Fujimura Akemi Sakamoto Masahiko Hatano Hirokuni Hirata Yasutsugu Fukushima Takeshi Fukuda Kazuhiro Kurasawa Koichiro Tatsumi Takeshi Tokuhisa Masafumi Arima Masafumi Arima Allergic TH2 Response Governed by B-Cell Lymphoma 6 Function in Naturally Occurring Memory Phenotype CD4+ T Cells Frontiers in Immunology B-cell lymphoma 6 naturally occurring memory phenotype T cells allergy TH2 cells asthma |
author_facet |
Takashi Ogasawara Yuko Kohashi Jun Ikari Toshibumi Taniguchi Nobuhide Tsuruoka Haruko Watanabe-Takano Lisa Fujimura Akemi Sakamoto Masahiko Hatano Hirokuni Hirata Yasutsugu Fukushima Takeshi Fukuda Kazuhiro Kurasawa Koichiro Tatsumi Takeshi Tokuhisa Masafumi Arima Masafumi Arima |
author_sort |
Takashi Ogasawara |
title |
Allergic TH2 Response Governed by B-Cell Lymphoma 6 Function in Naturally Occurring Memory Phenotype CD4+ T Cells |
title_short |
Allergic TH2 Response Governed by B-Cell Lymphoma 6 Function in Naturally Occurring Memory Phenotype CD4+ T Cells |
title_full |
Allergic TH2 Response Governed by B-Cell Lymphoma 6 Function in Naturally Occurring Memory Phenotype CD4+ T Cells |
title_fullStr |
Allergic TH2 Response Governed by B-Cell Lymphoma 6 Function in Naturally Occurring Memory Phenotype CD4+ T Cells |
title_full_unstemmed |
Allergic TH2 Response Governed by B-Cell Lymphoma 6 Function in Naturally Occurring Memory Phenotype CD4+ T Cells |
title_sort |
allergic th2 response governed by b-cell lymphoma 6 function in naturally occurring memory phenotype cd4+ t cells |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-04-01 |
description |
Transcriptional repressor B-cell lymphoma 6 (Bcl6) appears to regulate TH2 immune responses in allergies, but its precise role is unclear. We previously reported that Bcl6 suppressed IL-4 production in naïve CD4+ T cell-derived memory TH2 cells. To investigate Bcl6 function in allergic responses in naturally occurring memory phenotype CD4+ T (MPT) cells and their derived TH2 (MPTH2) cells, Bcl6-manipulated mice, highly conserved intron enhancer (hcIE)-deficient mice, and reporter mice for conserved noncoding sequence 2 (CNS2) 3′ distal enhancer region were used to elucidate Bcl6 function in MPT cells. The molecular mechanisms of Bcl6-mediated TH2 cytokine gene regulation were elucidated using cellular and molecular approaches. Bcl6 function in MPT cells was determined using adoptive transfer to naïve mice, which were assessed for allergic airway inflammation. Bcl6 suppressed IL-4 production in MPT and MPTH2 cells by suppressing CNS2 enhancer activity. Bcl6 downregulated Il4 expression in MPTH2 cells, but not MPT cells, by suppressing hcIE activity. The inhibitory functions of Bcl6 in MPT and MPTH2 cells attenuated allergic responses. Bcl6 is a critical regulator of IL-4 production by MPT and MPTH2 cells in TH2 immune responses related to the pathogenesis of allergies. |
topic |
B-cell lymphoma 6 naturally occurring memory phenotype T cells allergy TH2 cells asthma |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2018.00750/full |
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