1. Defective Treg generation and increased type 3 immune response in leukocyte adhesion deficiency 1.
- Author
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Erdem S, Haskologlu S, Haliloglu Y, Celikzencir H, Arik E, Keskin O, Eltan SB, Yucel E, Canatan H, Avcilar H, Yilmaz E, Ozcan A, Unal E, Karakukcu M, Celiksoy MH, Kilic SS, Demir A, Genel F, Gulez N, Koker MY, Ozen AO, Baris S, Metin A, Guner SN, Reisli I, Keles S, Dogu EF, Ikinciogullari KA, and Eken A
- Subjects
- Humans, Immunity, Innate, CD4-Positive T-Lymphocytes, Th17 Cells, T-Lymphocytes, Regulatory, Leukocyte-Adhesion Deficiency Syndrome
- Abstract
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., Competing Interests: Declaration of Competing Interest The authors declare no competing interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)- Published
- 2023
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