Activated unconventional T cells masquerade as innate lymphoid cells in the inflamed lungs

Innate lymphoid cells (ILCs) are central regulators of this balance. While pulmonary group 3 ILCs (ILC3) play both protective and pathogenic roles, their origins during inflammation remain unclear due to their scarcity in steady-state mouse lungs.

From Il-1β inflamed mouse lungs, we sort-purfied surface lineage negative CD127+ pan-ILCs, CD3+ TCRβ+ CD4- CD8- unconventional double-negative (DN) αβ T cells, conventional αβ T cells and γδ T cells and employed 10X Genomics scRNA-seq and paired TCR V(D)J profiling to explore the relationships between these cell types in the inflamed lung. We demonstrate that the pulmonary ILC3 population segregates into two distinct pools that show considerable transcriptional overlap with activated DN αβ T cells, specifically iNKT and MAIT cells.