353 Immunomodulatory role of NF-kB signalling pathway in skin inflammation
نویسندگان
چکیده
IKK/NF-kB signalling controls inflammation and cell death is important to maintain tissue homeostasis. Keratinocyte-specific deletion of IKK2 (IKK2E-KO) leads TNFR1-dependent skin in mice. IKK2E-KO mice showed increased numbers apoptotic necrotic keratinocytes, upregulation inflammatory cytokines mediators the epidermis. We proposed that keratinocyte could trigger inflammation. Receptor Interacting Protein Kinase (RIPK1) induces via kinase activity-dependent functions. To address kinase-dependent role RIPK1 mice, we generated expressing inactive (IKK2E-KO; Ripk1D138N/D138N). observed IKK2E-KO;Ripk1D138N/D138N did not develop lesions, demonstrating an essential activity further dissected whether apoptosis or necroptosis drives by crossing them lacking RIPK3 MLKL, which are necroptosis. found IKK2E-KO;Ripk3-/- IKK2E-KO;Mlkl-/- were strongly protected from lesion development, showing triggering dissect different components NF-kB pathway regulating homeostasis, with combined deficiency subunits, cRel RelA a regulatory subunit IKK complex, NEMO (NEMOE-KO) Both, cRel/RelAE-KO NEMOE-KO developed inflammation, however, RIPKI but These results highlight differential control homeostasis through unravel potential unknown controlling
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ژورنال
عنوان ژورنال: Journal of Investigative Dermatology
سال: 2022
ISSN: ['1523-1747', '0022-202X']
DOI: https://doi.org/10.1016/j.jid.2022.09.366