The SHP-1 protein encoded by the Ptpn6 gene has been extensively studied in hematopoietic cells in the context of inflammation.A point mutation in this gene(Ptpn6spin)causes spontaneous inflammation in mice,which has ...The SHP-1 protein encoded by the Ptpn6 gene has been extensively studied in hematopoietic cells in the context of inflammation.A point mutation in this gene(Ptpn6spin)causes spontaneous inflammation in mice,which has a striking similarity to neutrophilic dermatoses in humans.Recent findings highlighted the role of signaling adapters and kinases in promoting inflammation in Ptpn6spin mice;however,the underlying transcriptional regulation is poorly understood.Here,we report that SYK is important for driving neutrophil infiltration and initiating wound healing responses in Ptpn6spin mice.Moreover,we found that deletion of the transcription factor Ets2 in myeloid cells ameliorates cutaneous inflammatory disease in Ptpn6spin mice through transcriptional regulation of its target inflammatory genes.Furthermore,Ets-2 drives IL-1α-mediated inflammatory signaling in neutrophils of Ptpn6spin mice.Overall,in addition to its well-known role in driving inflammation in cancer,Ets-2 plays a major role in regulating IL-1α-driven Ptpn6spin-mediated neutrophilic dermatoses.展开更多
基金supported by the K22 NIAID Career Transition Award Al 127836 to P.G.,the National Institutes of Health grants CAI 63507,AR056296,Al 124346 and AI101935 and by the American Lebanese Syrian Associated Charities to T.-D.K。
文摘The SHP-1 protein encoded by the Ptpn6 gene has been extensively studied in hematopoietic cells in the context of inflammation.A point mutation in this gene(Ptpn6spin)causes spontaneous inflammation in mice,which has a striking similarity to neutrophilic dermatoses in humans.Recent findings highlighted the role of signaling adapters and kinases in promoting inflammation in Ptpn6spin mice;however,the underlying transcriptional regulation is poorly understood.Here,we report that SYK is important for driving neutrophil infiltration and initiating wound healing responses in Ptpn6spin mice.Moreover,we found that deletion of the transcription factor Ets2 in myeloid cells ameliorates cutaneous inflammatory disease in Ptpn6spin mice through transcriptional regulation of its target inflammatory genes.Furthermore,Ets-2 drives IL-1α-mediated inflammatory signaling in neutrophils of Ptpn6spin mice.Overall,in addition to its well-known role in driving inflammation in cancer,Ets-2 plays a major role in regulating IL-1α-driven Ptpn6spin-mediated neutrophilic dermatoses.
