Bhattacharya, Shreya Kim, Jin-Chul Ogawa, Youichi Nakato, Gaku Nagle, Veronica Brooks, Stephen R. Udey, Mark C. Morasso, Maria I. 2024-01-19T23:00:34Z 2024-01-19T23:00:34Z 2021-09-03 2018-05 0022-202X https://pubs.kist.re.kr/handle/201004/121416 Epidermal-specific deletion of the homeobox transcription regulator DLX3 disrupts keratinocyte differentiation and results in an IL-17-linked psoriasis-like skin inflammation. To identify the epidermal initiating signals produced by DLX3-null keratinocytes, we performed acute deletion of DLX3 in adult epidermis using a tamoxifen-inducible Krt14-cre/ERT system. K14CreERT;DLX3(fl/fl) skin exhibited dysregulated expression of differentiation-associated genes, upregulation of proinflammatory cytokines, and accumulation of Langerhans cells and macrophages within 3 days of tamoxifen-induced DLX3 ablation. We also observed increased accumulation of IL-17A-secreting V gamma 4 gamma delta T cells and heightened levels of IL-17 and IL-36 family of cytokines starting 1 week after DLX3 deletion. Interestingly, transcriptome profiling of K14CreERT;DLX3(fl/fl) epidermis at 3 days identified activated STAT3 as a transcriptional regulator and revealed differential expression of STAT3 signaling-related genes. Furthermore, activation of STAT3 was strongly increased in K14CreERT;DLX3(fl/fl) skin, and topical treatment with an inhibitor of STAT3 activation attenuated the immune phenotype. RNA-seq analysis of vehicle and STAT3 inhibitor treated K14CreERT;DLX3(fl/fl) skin identified differentially expressed genes associated with inhibition of leukocyte infiltration. Collectively, our results show that DLX3 is a critical regulator of STAT3 signaling network that maintains skin homeostasis. English ELSEVIER SCIENCE INC CORNIFIED ENVELOPE LANGERHANS CELLS T-CELLS TRICHODENTOOSSEOUS SYNDROME EPIDERMAL DIFFERENTIATION SUSCEPTIBILITY LOCI BARRIER FUNCTION GENE-EXPRESSION DEFICIENT MICE HAIR FOLLICLE DLX3-Dependent STAT3 Signaling in Keratinocytes Regulates Skin Immune Homeostasis Article 10.1016/j.jid.2017.11.033 1 JOURNAL OF INVESTIGATIVE DERMATOLOGY, v.138, no.5, pp.1052 - 1061 JOURNAL OF INVESTIGATIVE DERMATOLOGY 138 5 1052 1061 scie scopus 000430533700022 Dermatology Dermatology Article CORNIFIED ENVELOPE LANGERHANS CELLS T-CELLS TRICHODENTOOSSEOUS SYNDROME EPIDERMAL DIFFERENTIATION SUSCEPTIBILITY LOCI BARRIER FUNCTION GENE-EXPRESSION DEFICIENT MICE HAIR FOLLICLE