Keratinocytes are the predominant cell type ofthe human skin. Their primary function is the formation of a barrier against environmental damage such as UV radiation and pathogens. However, the extent of the Keratinocyte contribution to innate immune host defense is still elusive. A major breakthrough came from demonstrating the existence of a NLRP1 inflammasome in Keratinocytes, which senses cellular stress caused by UVB exposure, resulting in the release of interleukin (IL)-ip and subsequent local inflammation to initiate wound healing. Inflammasomes have been mainly described in macrophages and represent an innate immune host defense system linking pathogen and stress recognition by cytosolic pattern recognition receptors (PRRs) of the Nod-like receptor (NLR) family to the activation of caspase-1-dependent processing and release of the inflammatory cytokines IL-1B and IL-18(2). The NLR family consists of 22 members with tripartite domain architecture of a C-terminal leucine rich region (LRR), a central nucleotide binding NACHT domain, and an N-terminal effector domain crucial for downstream signaling, which is a PYRIN domain (PYD) in most NLRs and are referred to as NLRPs(3). Pathogen sensing occurs by the LRRs and results inreceptor oligomerization and recruitment of the adaptor protein ASC, which subsequently bridges NLRs to the activation of caspase-1(4,5). Since NLRP1 senses UV radiation it is feasible that other NLRs are present in Keratinocyes to allow pathogen recognition, inflammasome activation and subsequently an innate immune host defense that promotes pathogen clearance.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Center Core Grants (P30)
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Special Emphasis Panel (ZAR1-KM-D (M1))
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Northwestern University at Chicago
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