Defective Treg generation and increased type 3 immune response in leukocyte adhesion deficiency 1

Erdem S., HASKOLOĞLU Z. Ş., Haliloglu Y., Celikzencir H., Arik E., Keskin O., ...More

Clinical Immunology, vol.253, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 253
  • Publication Date: 2023
  • Doi Number: 10.1016/j.clim.2023.109691
  • Journal Name: Clinical Immunology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Keywords: ILC, LAD-1, Leukocyte adhesion deficiency, Th17, Treg
  • Istanbul University Affiliated: Yes


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.