RAG1 deficiency durably alters dermal group 2 innate lymphoid cells and modifies contact hypersensitivity.

INTRODUCTION

Dermal group 2 innate lymphoid cells (dILC2s) contribute to skin homeostasis and inflammatory responses, yet they are frequently studied in Rag1-deficient mice in which the dILC2 compartment may itself be altered.

METHODS

We compared dILC2s from wild-type (WT) and Rag1-deficient mice by transcriptomic profiling, flow cytometric phenotyping, and functional analysis in a DNFB-induced contact hypersensitivity model with short-term adoptive lymphocyte transfer.

RESULTS

Rag1 deficiency was associated with a marked expansion of dILC2s and broad transcriptional remodeling, including increased expression of Il7r, Thy1, Il5, and Il13, together with enrichment of cytokine signaling, apoptosis, and activation pathways. In vivo, Rag1-deficient mice showed attenuated ear swelling after DNFB challenge and, in contrast to WT mice, failed to expand their absolute dILC2 abundance during inflammation. Short-term adoptive transfer of sensitized WT lymphocytes modestly modified dILC2 dynamics but did not restore the WT inflammatory phenotype. At the cellular level, Rag1-deficient dILC2s displayed a predominantly CD44hi phenotype, increased basal apoptosis, elevated caspase-3/7 activity, and increased BrdU incorporation.

DISCUSSION: Together, these findings show that Rag1 deficiency durably alters dILC2 state and responsiveness and should be taken into account when interpreting cutaneous inflammation models in immunodeficient mice.