Get started
Work

Group 3 innate lymhoid cells are absent in DOCK8-defective HIES patients

Year: 2018
Type: conference-abstract
Abstract: Innate lymphoid cell (ILC) subsets ILC1, ILC2 and ILC3 mirror image the functions helper CD4+ T cell subsets, Th1, Th2 and Th17, respectively; rely on similar transcription factors for their development, and produce similar effector cytokines. Thus, they have recently been shown to be crucial for protective immunity in mice. More importantly, in several chronic inflammatory diseases activated or increased frequency of ILCs have been reported in the circulation or affected tissues of patients. Our previous work with Dock8-defective Dock8pri/pri mice revealed that Dock8 is required for the development/function and survival of murine ILC3s. Thus Dock8pri/pri mice lacked ILC3s and was susceptible to Citrobacter rodentium infections. However to date, whether DOCK8 regulates ILC3 development or functions in humans has not been addressed. In the current study, using 11 DOCK8 mutant patients from across Turkey, we show, for the first time, that humans with DOKC8 deficiency lack peripheral ILC3s. Reduction in blood ILC3 could be verified by flow cytometry. Additionally, sorted total blood ILC population obtained from HIES patients with DOCK8 mutations shows diminished ILC3-specific Gm-csf, AhR and il23r gene expression in line with ILC3 loss. The defect is dramatic in ILC3s and less so in ILC2s in circulation. Flow cytometric examination of 11 patients revealed full restroration of ILC3s following hematopoietic stem cell transplantation. We also show that sorted peripheral ILC precursor population obtained from DOCK8 mutant patients has impaired capacity to proliferate in ILC1-ILC2-ILC3 polarizing conditions. This is the first report in the literature to show a selective deletion of ILC3s in HIES patients with DOCK8 mutations.
DOI: 10.4049/jimmunol.200.supp.170.25
Authors: Ahmet Eken, Fatma Zehra Okus, Turkan Patiroglu, Serife Erdem, Musa Karakukcu, Murat Cansever, Hamiyet Donmez-Altuntas, Halit Canatan, Mohamed Oukka, Erdem Topal, Ayca Kiyim, Elif Karakoc, Ayse Metin, Ismail Reisli, Vedat Uygun, Safa Baris, Sevgi Keles, Ahmet Ozen, Gulsun Karasu, Ekrem Unal
Institutions: Erciyes University, University of Washington, Inonu University, Marmara University, Hacettepe University, Necmettin Erbakan University
Language: English
Subfield: Immunology
Open Access status: green
OpenAlex ID: W4313359169
Cites:
Cited by:
Related to: 10