Erdem, Serife, Haskologlu, Sule, Haliloglu, Yesim, Celikzencir, Huriye, Arik, Elif, Keskin, Ozlem, Eltan, Sevgi Bilgic, Yucel, Esra, Canatan, Halit, Avcilar, Huseyin, Yilmaz, Ebru, Ozcan, Alper, Unal, Ekrem, Karakukcu, Musa, Celiksoy, Mehmet Halil, Kilic, Sara Sebnem, Demir, Ayca, Genel, Ferah, Gulez, Nesrin, and Koker, Mustafa Yavuz
In 15 Turkish LAD-1 patients and controls, we assessed the impact of pathogenic ITGB2 mutations on Th17/Treg differentiation and functions, and innate lymphoid cell (ILC) subsets. The percentage of peripheral blood Treg cells, in vitro- generated induced Tregs differentiated from naive CD4+ T cells were decreased despite the elevated absolute counts of CD4+ cells in LAD-1 patients. Serum IL-23 levels were elevated in LAD-1 patients. Post-curdlan stimulation, LAD-1 patient-derived PBMCs produced more IL-17A. Additionally, the percentages of CD18-deficient Th17 cells expanded from total or naïve CD4+ T cells were higher. The blood ILC3 subset was significantly elevated in LAD-1. Finally, LAD-1 PBMCs showed defects in trans-well migration and proliferation and were more resistant to apoptosis. Defects in de novo generation of Tregs from CD18-deficient naïve T cells and elevated Th17s, and ILC3s in LAD-1 patients' peripheral blood suggest a type 3-skewed immunity and may contribute to LAD-1-associated autoimmune symptoms. • The frequency of Treg cells but not the absolute number is reduced in LAD-1 peripheral blood. • De novo Treg differentiation of CD18-deficient human naïve CD4+ T cells is reduced. • Serum IL-23 level and peripheral blood ILC3 subset are elevated in LAD-1 patients. • Percentages of Th17 cells expanded from total LAD-1 patient-derived CD4+ T cells are higher. • LAD-1 PBMCs showed defective trans-well migration and proliferation, and were resistant to apoptosis. [ABSTRACT FROM AUTHOR]