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Ryser, S., Schuppli, M., & Gauthier, B. (2014). UVB-Induced Skin Inflammation and Cutaneous Tissue Injury Is Dependent on the MHC Class I–Like Protein, CD1d. Journal of Investigative Dermatology, 134(1), 192–202. 
Added by: Dr. Enrique Feoli (23/11/2023, 12:54)   Last edited by: Dr. Enrique Feoli (05/12/2023, 19:42)
Resource type: Journal Article
DOI: 10.1038/jid.2013.300
ID no. (ISBN etc.): 0022-202X, 1523-1747
BibTeX citation key: Ryser2014
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 Categories: BioAcyl Corp
Subcategories: UV Damage Repair
Creators: Gauthier, Ryser, Schuppli
Collection: Journal of Investigative Dermatology		 Views: 3/254
Abstract
CD1d is a major histocompatibility complex class 1–like molecule that regulates the function and development of natural killer T (NKT) cells. Previously, we identified a critical role for the CD1d-NKT cell arm of innate immunity in promoting the development of UVB-induced p53 mutations, immune suppression, and skin tumors. Sunburn, an acute inflammatory response to UVB-induced cutaneous tissue injury, represents a clinical marker for non-melanoma skin cancer (NMSC) risk. However, the innate immune mechanisms controlling sunburn development are not considered relevant in NMSC etiology, and remain poorly investigated. Here we found that CD1d knockout (CD1d−/−) mice resist UVB-induced cutaneous tissue injury and inflammation compared with wild-type (WT) mice. This resistance was coupled with a faster epithelial tissue healing response. In contrast, the skins of UVB-irradiated invariant NKT cell-knockout (Jα18−/−) and NKT cell–deficient (TCRα−/−) mice, which express CD1d but are deficient in CD1d-dependent NKT cells, exhibited as much cutaneous tissue injury and inflammation as WT mice. In the absence of NKT cells, CD1d-deficient keratinocytes, dendritic cells, and macrophages exhibited diminished basal and stress-induced levels of pro-inflammatory mediators. Thus, our findings identify an essential role for CD1d in promoting UVB-induced cutaneous tissue injury and inflammation. They also suggest sunburn and NMSC etiologies are immunologically linked.
  
Notes

  • Invariant natural killer T (iNKT) cells are a specialized T cell population that recognizes lipid antigens that are presented by a cell-surface molecule known as CD1d. They have been shown to have important roles in many diverse immune responses.

  • iNKT cells recognize both foreign lipid antigens and self lipid antigens. The T cell receptor (TCR)–lipid–CD1d interaction is similar for both self and foreign lipid antigens, despite the differences that exist in these lipid structures. Strong lipid antigens have a 'lock and key' type of binding, whereas weaker antigens require an 'induced fit' mechanism.

  • The production of lipid self antigens for iNKT cells can be upregulated by antigen-presenting cells (APCs) in response to danger signals, such as Toll-like receptor (TLR) agonists. This provides a mechanism for iNKT cell activation in the absence of foreign lipid antigens.

  • In addition to being activated through their TCRs in response to CD1d-presented lipids, iNKT cells can be activated by indirect stimuli, such as pro-inflammatory cytokines. During many infections, interleukin-12 (IL-12) may have an equally important role to lipid antigens in activating iNKT cells.

  • iNKT cells couple the rapid activation kinetics of innate immune cells with the diverse effector functions of adaptive T cells. Early activation during infection leads to rapid cytokine production in target tissues by polarized iNKT cell subsets.

  • Interactions between iNKT cells and CD1d-expressing APCs lead to bidirectional activation. Cytokines produced by iNKT cells activate and recruit other cell types early during immune responses, while activated APCs direct the ensuing adaptive immune responses. Thus, iNKT cells and their lipid antigens help to orchestrate innate and adaptive immune responses.

https://www.nature.com/articles/nri3369


Added by: Dr. Enrique Feoli  Last edited by: Dr. Enrique Feoli
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