T-bet and STAT6 Coordinately Suppress the Development of IL-9-Mediated Atopic Dermatitis-Like Skin Inflammation in Mice

被引：7

作者：

Makita, Sohei ^{[1
]}

Takatori, Hiroaki ^{[1
,2
]}

Matsuki, Ayako ^{[1
]}

Kawashima, Hirotoshi ^{[1
,3
]}

Iwata, Arifumi ^{[1
]}

Tanaka, Shigeru ^{[1
]}

Nakagomi, Daiki ^{[4
]}

Oya, Yoshihiro ^{[5
]}

Matsumura, Ryutaro ^{[5
]}

Tamachi, Tomohiro ^{[1
]}

Suto, Akira ^{[1
]}

Suzuki, Kotaro ^{[1
]}

Hirose, Koichi ^{[1
,3
]}

Nakajima, Hiroshi ^{[1
]}

机构：

[1] Chiba Univ, Grad Sch Med, Dept Allergy & Clin Immunol, 1-8-1 Inohana, Chiba, Chiba 2608670, Japan

[2] Hamamatsu Med Ctr, Dept Rheumatol, Shizuoka, Japan

[3] Int Univ Hlth & Welf, Sch Med, Dept Rheumatol, Chiba, Japan

[4] Yamanashi Univ, Dept Internal Med 3, Kofu, Yamanashi, Japan

[5] Natl Hosp Org Chibahigashi Natl Hosp, Dept Rheumatol Allergy & Clin Immunol, Chiba, Japan

来源：

JOURNAL OF INVESTIGATIVE DERMATOLOGY | 2021年 / 141卷 / 05期

关键词：

CELL-DIFFERENTIATION; TH9; CELLS; INTERLEUKIN-9; EXPRESSION; ASTHMA; T(H)2;

D O I：

10.1016/j.jid.2020.08.029

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

T-bet and signal transducer and activator of transcription (STAT) 6 are critical factors for helper T-cell differentiation in humans and mice. Additionally, polymorphisms in TBX21 (T-bet) and STAT6 are associated with the susceptibility of allergic diseases. However, precise mechanisms of the reciprocal regulation between T-bet and STAT6 in allergy remain unclear. To determine the reciprocal regulation in vivo, we investigated the phenotype of T-bet/STAT6 double-deficient (T -bet(-/-) STAT6(-/-)) mice. Unexpectedly, T-bet(-/-) STAT6(-/-) mice but not T bet(-/-) miceor STAT6(-/-) mice spontaneously developed severe dermatitis. Not only eosinophils and mast cells but also CD4+ T cells infiltrated into the skin of T-bet(-/-) STAT6(-/-) mice. Adoptive transfer of CD4(+) T cells of T bet(-/-) STAT6(-/-) miceinto severe combined immunodeficient mice induced the accumulation of eosinophils and mast cells in the skin, whereas depletion of CD4(+) T cells ameliorated the dermatitis in T-bet(-/-) STAT6(-/-) mice. Comprehensive transcriptome analyses revealed that IL-9 expression was enhanced in T-bet(-/-) STAT6(-/-) CD4(+) T cells. Indeed, IL-9 neutralization ameliorated the dermatitis in T-bet(-/-) STAT6-/- mice. T-bet(-/-) STAT6(-/-) CD4(+) T cells expressed functional thymic stromal lymphopoietin receptors and produced large amounts of IL-9 on thymic stromal lymphopoietin stimulation. These results indicate that T-bet and STAT6 coordinately suppress atopic dermatitis-like skin inflammation, possibly by inhibiting thymic stromal lymphopoietin-dependent IL-9 production in CD4(+) T cells.

引用

页码：1274 / +

页数：17

共 38 条

[1] Th9 Cells in Allergic Disease [J].