Innate Lymphoid Cells Are the Rheostat of Immune Response in the Kidney.

Kidney disease ranks as the seventh most significant and the third fastest-growing risk factor contributing to mortality globally. Innate lymphoid cells (ILCs) are tissue-resident immune cells that lack antigen-specific receptors and produce robust cytokines. ILCs play vital roles in infection, allergy, metabolic disorders, cancers, and tissue homeostasis. Recent studies have found that ILCs are manipulated for various kidney diseases. ILCs are classified into natural killer (NK) cells, ILC1s, ILC2s, ILC3s, and regulatory ILCs (ILCregs). We mainly discuss ILC1s, ILC2s, and ILC3s in kidney diseases. ILC2s and ILC3s are distributed along the renal vessels, and ILC3s are involved in the formation of ectopic lymphoid structures. ILCs secrete a variety of active cytokines, which can directly act on renal parenchymal cells or recruit other immune cells to affect kidney disease. Both acute kidney injury (AKI) and chronic kidney disease (CKD) are regulated by ILCs. ILC2s play a protective role in AKI and glomerulonephritis. Though ILC3s promote fibrosis in CKD, the roles of ILC2s in kidney fibrosis remain controversial. ILC1s and ILC3s promote glomerulonephritis. Kidney diseases will benefit from further studies focusing on the epigenetic/metabolic/neuron modulation and plasticity of ILCs.