CD1a function in human skin disease

Abstract

The high expression of CD1a on Langerhans cells in normal human skin suggests a central role for this lipid antigen presenting molecule in skin homeostasis and immunity. Although the lipid antigen presenting function of CD1a has been known for years, the physiological and pathological functions of the CD1a system in human skin remain incompletely understood. This review provides an overview of this active area of investigation, and discusses recent insights into the functions of CD1a, CD1a-restricted T cells, and lipid antigens in inflammatory and allergic skin disease. We include recent publications and work presented at the biennial CD1-MR1 EMBO workshop held in 2019 in Oxford, regarding lipids that increase and those that decrease T cell responses to CD1a.

Keywords: CD1 antigen presenting molecules; Lipids; Skin; T cells.

Figure 1.. CD1a and lipid recognition in human skin.

Langerhans cells (LC) are in close proximity to the skin microbiome. A subset of human T cells recognizes a bacterial phospholipid in the context of CD1a. Another subset of skin T cells is CD1a-autoreactive and primarily interacts with CD1a, rather than the lipid bound. Permissive lipids allow the interaction between autoreactive TCR and CD1a, whereas inhibitor lipids prevent this interaction. PLA2 from exogenous or endogenous sources, such as house dust mite, mast cells, respectively, cleaves membrane phospholipids, yielding permissive lipids and augmenting CD1a-autoreactive T cell responses. Certain contact allergens such as farnesol have been shown to displace resident lipids, enabling TCR-CD1a interactions (Nicolai et al., 2020). LC Langerhans cell, PLA2 Phospholipase A2, SM Sphingomyelin, SLF Sulfatide, FN Farnesol (contact allergen), WE Wax ester, FA Fatty acid, LPC Lysophosphatidylcholine, SQ Squalene.