701 High dimensional peripheral blood immune cell profiling of atopic dermatitis patients unveiled IL21 cytokine activation

Abstract

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease affecting 7% of adults in the United States. While skin and blood profiling of AD primarily highlighted its Th2/ -skewing, novel Th2-targeting strategies are able to induce clearance in <40% of moderate-to-severe patients. To expand upon the current knowledge on the systemic immune activation of AD, we measured the frequencies of 13 cytokines, 4 transcription factors and activation markers in circulating skin-homing (CLA+) and systemic (CLA-) CD4+/CD8+ activated T-cell subsets using mass cytometry or CyTOF, that allows simultaneous profiling of more than 40 markers. High profiling mass cytometry enabled us to measure not only the defining Th/Tc cytokines Th/c1/IFN-g/Th/c2/IL-13/Th/c17/IL-17A/Th/c22/IL-22,Th/c/IL-9 in CD4+/CD8+ T-cells but also TNFa/GM-CSF/IL-2/IL-4/IL-5/IL-31/IL-10/IL-21 producing T cells in blood of moderate-to-severe AD patients (n=20) and controls (n=15). These cytokine-producing T-cell subsets were also highly correlated with disease severity (SCORAD). In addition to the Th2/Tc2 and Th22/Tc22 polarization, the blood of AD patients was characterized by significant increases in IL21 producing CD4+/CD8+ T-cells (p<0.01) in both CLA+/CLA- compartments. IL-21 production was primarily detected among Th/c2 and Th/c22 in AD but not in control subjects, as well as in a unique population that mainly produces IL-21. Positive correlations with SCORAD were observed in CLA+IL21+CD4+/CD8+ T cells (r=0.61; p<0.01). The frequency of these CLA+IL21+CD4+/CD8+ T cells was also correlated with that of the CLA+Th/c2/Th/c22 cells (p<0.001), suggesting the Th/c2/Th/c22 as potentially the source of IL21 in AD. In conclusion, high dimensional profiling of peripheral blood with mass cytometry revealed a possible role of systemic IL21-skewing in moderate-to-severe AD.