Unravelling γδ T-cell dysregulation in the gut and its implications for immune-mediated diseases.

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and characterised by systemic inflammation and T-cell dysfunction. A subset of patients with MIS-C were found to harbour rare variants in the gene BTNL8 that disrupt BTNL8-BTNL3 heterodimer formation, likely leading to inadequate γδ T-cell regulation and subsequent disrupted gut homeostasis. MIS-C shares clinical features with Kawasaki disease and similar mechanisms of pathogenesis with inflammatory bowel disease, despite these diseases being clinically distinct entities. We explore the common link between these diseases: the potentially critical role gut immunity plays in the initiation and persistence of disease through the tight regulation of γδ T cells via BTNL8 and BTNL3. Understanding the role of BTNL8 in the context of the overlap between these conditions may aid preventative measures and treatment of these conditions.