Ets-2 deletion in myeloid cells attenuates IL-1α-mediated inflammatory disease caused by a Ptpn6 point mutation  

作　　者：Sarang Tartey Prajwal Gurung Rajendra Karki Amanda Burton Paul Hertzog Thirumala-Devi Kanneganti 

机构地区：[1]Department of Immunology,St.Jude Children’s Research Hospital,Memphis,TN,38105,USA [2]Inflammation Program,University of Iowa,Iowa City,IA,52241,USA [3]Centre for Innate Immunity&Infectious Diseases,Hudson Institute of Medical Research,Department of Molecular and Translational Sciences,Monash University,Clayton,Victoria,3168,Australia

出　　处：《Cellular & Molecular Immunology》2021年第7期1798-1808,共11页中国免疫学杂志（英文版）

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。

摘　　要：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.

关 键 词：AUTOINFLAMMATION ETS-2 IL-1Α Neutrophilic dermatoses PTPN6 SHP-1 

分 类 号：R392[医药卫生—免疫学]