Phenotypic shift of small intestinal intraepithelial type 1 innate lymphoid cells in celiac disease is associated with enhanced cytotoxic potential.

We report that duodenal intraepithelial ILCs predominantly consist of NKp44+ CD127- cytotoxic ILC1s and NKp44- CD127+ helper ILC1s, while ILC3s only represent a minor population. In patients with newly diagnosed or active CD (ACD) and refractory CD type 1 (RCD I), the frequency of SI NKp44+ ILCs is decreased, with restoration of NKp44+ ILC frequency observed in patients adhering to a gluten-free diet who show evidence of mucosal healing. On the other hand, the frequency of SI NKp44- ILCs is increased in ACD and RCD I patients and correlates with increased severity of villous atrophy and epithelial damage, as assessed by serum levels of fatty acid binding protein 2 (FABP2). We show that the ILC alterations in CD represent a phenotypic shift of cytotoxic ILC1s rather than an increase in helper ILC1s or transdifferentiation to ILC3s and activation-induced loss of NKp44 by cytotoxic ILC1s is associated with increased IFN-γ expression and release of lytic granules. These findings suggest that intraepithelial NKp44- CD127- cytotoxic ILC1s may contribute to mucosal damage in ACD and RCD I. PMID: 31907928 [PubMed - as supplied by publisher]
Source: Clinical and Developmental Immunology - Category: Allergy & Immunology Authors: Tags: Clin Exp Immunol Source Type: research