Regulation of Th1 proinflammatory response via the complosome in patients with allergic eosinophilic asthma



Year of publication 2022
Type Conference abstract
MU Faculty or unit

Faculty of Medicine

Description Allergic eosinophilic asthma (AEA) is considered to be one of the most common types of asthma representing approximately 75 % of all cases. Th2 mediated inflammation is assumed to be the main immunopathological mechanism of AEA, however recent studies indicate that impaired Th1 response might also contribute to the diagnosis of AEA. Since Th1 response is critically regulated by an intracellular complement system - the complosome, we focused to the complosome driven INF-?/IL-10 switch in patients with AEA. The complosome driven INF-?/IL-10 switch is typically associated with an elevation of IL-10+ regulatory T-cells (Tr1). Previous studies have already confirmed an increased INF-? levels in bronchoalveolar lavage and decreased serum levels of IL-10 in AEA patients, but the main immunopathological mechanism remains unknown. We assume a possible defect in a complosome driven INF-?/IL-10 switch, which might be positively influenced by calcitriol (active form of vitamin D) administration. Isolated CD4+ T-cells from whole blood were stimulated with a combination of anti-CD3, anti-CD46, IL-2 and calcitriol or ethanol as a vehicle control for 60 hours. Stimulated CD4+ T-cells were stained for flow cytometry with a combination of following markers: CD4, CD46, C3b, C3aR, C5aR, CD25, Ki-67, INF-? and IL-10. Four T-cell subsets were distinguished based on cytokine secretion profile: INF-?-IL-10-, INF-?+IL-10-, INF-?+IL-10+ and INF-?-IL-10+ CD4 T-cells. Median fluorescence intensity and percentage of positive cells were analyzed for each marker. We confirmed that patients with AEA respond to the calcitriol administration differently and can be divided into two groups. Group A (52 % of AEA patients) which significantly increased IL-10+ Tr1 cells (? 8 % of total CD4 T-cells) and group B (48 % of AEA patients) which decreased IL-10+ Tr1 cells (< 8 % of total CD4 T-cells) after calcitriol administration when compared with healthy donors (HD). The complosome analysis (CD46, C3b, C3aR, C5aR) on CD4 T-cell subsets revealed that patients with AEA have similar expression of all markers when compared with HD. We observed no major difference in the complosome dynamics in AEA patients, therefore we can refute the first part of our hypothesis; the disrupted cytokine profile in AEA patients is complosome independent. However, group A of AEA patients positively responded to vitamin D administration. This group of patient might be promising for calcitriol supplementation with possible reduction of inflammation in airways.
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