Inflammation-induced remodeling

Cell https://doi.org/10.1016/j.cell.2018.12.039 (2019)

Mouse γδ T cells seed the intestine early in life and persist as intra-epithelial lymphocytes (IELs). In Cell, Jabri and colleagues show that a population of NKp46^–IFN-γ⁺V_γ1⁺ IELs accumulates in the small intestine of patients with celiac disease (CeD), but not those on a gluten-free diet, at the expense of the innate-like, cytotoxic NKp46⁺NKp44⁺V_γ1⁺ IELs found in healthy control subjects. NKp46^–V_γ1⁺ IELs from patients with CeD have a transcriptional program distinct from that of NKp46⁺V_γ1⁺ IELs from healthy subjects, irrespective of adherence to a gluten-free diet. V_γ1⁺ IELs from healthy subjects show enrichment for transcripts encoding the TCR γ-chain variable region 4, express genes encoding molecules associated with tissue repair and are reactive to the butyrophilin-like molecules BTNL3 and BTNL8, while NKp46^–V_γ1⁺ IELs from patients with CeD lack all those characteristics, even after restauration of expression of BTNL3 and BTNL8 in patients on a gluten-free diet. Thus, gluten-induced inflammation remodels the V_γ1⁺ IEL compartment, with consequences for tissue pathology.