The following is a summary of “Epicutaneous allergen immunotherapy induces a profound and selective modulation in skin dendritic-cell subsets,” published in the November 2022 issue of the Allergy and clinical immunology by Laoubi, et al.
Recently, epicutaneous immunotherapy (EPIT) procedures have been devised to help patients with food allergies regain their tolerance. The EPIT treatments’ desensitization-promoting processes rely on a serious immunological deviation of pathogenic T- and B-cell responses. The role of skin dendritic cells (skDCs) in T-cell remodeling and EPIT effectiveness needed to be better understood.
Researchers used a preclinical model of ovalbumin (OVA) food allergy to describe the phenotype and roles of OVA+ skDCs throughout EPIT.
The findings demonstrated that during EPIT, Langerhans cells and conventional dermal cDC1 and cDC2 subsets maintained their capacity to bind OVA in the skin and move in the direction of the skin-draining lymph nodes. However, as indicated by the progressive and targeted decrease of CD86, CD40, and OVA protein expression in corresponding subsets, their activation/maturation status was considerably compromised. Additionally, a gradual diversification of single-cell gene signatures within each DC subgroup described the phenotypic alterations that occurred during EPIT. They saw an interesting phenomenon where OVA+ Langerhans cells gradually lost their ability to prime CD4+ TEFF cells but gradually developed regulatory T-cell stimulatory capabilities. In contrast, cDC1 was ineffective for priming CD4+ TEFF cells or reactivating TMEM cells in vitro, but cDC2 maintained modest stimulatory qualities and progressively skewed type 2 immunity toward type 1 and type 17 responses.
Therefore, the findings highlighted that the fundamental component of the desensitization process was the skDCs’ acquisition of distinctive phenotypic and functional specializations during EPIT.