| First Author | Makita S | Year | 2021 |
| Journal | J Invest Dermatol | Volume | 141 |
| Issue | 5 | Pages | 1274-1285.e5 |
| PubMed ID | 33068596 | Mgi Jnum | J:311693 |
| Mgi Id | MGI:6709819 | Doi | 10.1016/j.jid.2020.08.029 |
| Citation | Makita S, et al. (2021) T-bet and STAT6 Coordinately Suppress the Development of IL-9-Mediated Atopic Dermatitis-Like Skin Inflammation in Mice. J Invest Dermatol 141(5):1274-1285.e5 |
| abstractText | 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(-/-) mice or 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(-/-) mice into 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. |
