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Front Immunol. 2018 Apr 10;9:750. doi: 10.3389/fimmu.2018.00750. eCollection 2018.

Allergic TH2 Response Governed by B-Cell Lymphoma 6 Function in Naturally Occurring Memory Phenotype CD4+ T Cells.

Author information

1
Department of Respirology (B2), Chiba University Graduate School of Medicine, Chiba, Japan.
2
Department of Biomedical Science (M14), Chiba University Graduate School of Medicine, Chiba, Japan.
3
Department of Reproductive Medicine (G4), Chiba University Graduate School of Medicine, Chiba, Japan.
4
Biomedical Research Center, Chiba University, Chiba, Japan.
5
Department of Respiratory Medicine and Clinical Immunology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan.
6
Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, Mibu, Japan.
7
Department of Rheumatology, Dokkyo Medical University School of Medicine, Mibu, Japan.
8
Department of Developmental Genetics, Chiba University Graduate School of Medicine, Chiba, Japan.

Abstract

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.

KEYWORDS:

B-cell lymphoma 6; TH2 cells; allergy; asthma; naturally occurring memory phenotype T cells

PMID:
29696026
PMCID:
PMC5904433
DOI:
10.3389/fimmu.2018.00750
[Indexed for MEDLINE]
Free PMC Article

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