Defective Treg generation and increased type 3 immune response in leukocyte adhesion deficiency 1
Creators
- Erdem, Serife
- Haskologlu, Sule1
- Haliloglu, Yesim
- Celikzencir, Huriye2
- Arik, Elif3
- Keskin, Ozlem3
- Eltan, Sevgi Bilgic4
- Yucel, Esra5
- Canatan, Halit
- Avcilar, Huseyin6
- Yilmaz, Ebru7
- Ozcan, Alper7
- Unal, Ekrem
- Karakukcu, Musa7
- Celiksoy, Mehmet Halil8
- Kilic, Sara Sebnem9
- Demir, Ayca
- Genel, Ferah
- Gulez, Nesrin10
- Koker, Mustafa Yavuz2
- 1. Ankara Univ, Dept Pediat Allergy & Immunol, Sch Med, Ankara, Turkiye
- 2. Erciyes Univ, Dept Immunol, Sch Med, Kayseri, Turkiye
- 3. Gaziantep Univ, Dept Pediat Allergy & Immunol, Sch Med, Gaziantep, Turkiye
- 4. Marmara Univ, Dept Pediat Allergy & Immunol, Sch Med, Istanbul, Turkiye
- 5. Istanbul Univ, Dept Pediat Allergy & Immunol, Sch Med, Istanbul, Turkiye
- 6. Erciyes Univ, Betul Ziya Eren Genome & Stem Cell Ctr, Kayseri, Turkiye
- 7. Erciyes Univ, Dept Pediat Hematol & Oncol, Sch Med, Kayseri, Turkiye
- 8. Univ Hlth Sci, Istanbul Basaksehir Cam & Sakura City Hosp, Pediat Allergy & Immunol Clin, Istanbul, Turkiye
- 9. Bursa Uludag Univ, Sch Med, Dept Pediat Immunol & Rheumatol, Bursa, Turkiye
- 10. Univ Hlth Sci, Dr Behcet Uz Childrens Educ & Res Hosp, Dept Pediat Allergy & Immunol, Izmir, Turkiye
Description
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 naive 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 naive T cells and elevated Th17s, and ILC3s in LAD1 patients' peripheral blood suggest a type 3-skewed immunity and may contribute to LAD-1-associated autoimmune symptoms.
Files
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