The annual incidence of kidney disease is increasing and is becoming a major global public health issue that imposes a heavy burden on society and families. However, the complex pathogenesis of kidney disease is not yet fully understood. The immune system is closely linked to kidney diseases and plays a pivotal role in the onset and progression of acute and chronic kidney diseases. Recent studies have revealed that innate and adaptive immune cells substantially influence the development of both acute and chronic kidney diseases. Elucidating the role of innate lymphoid cells (ILCs) in kidney disease may provide novel therapeutic targets and open new treatment avenues. This review summarises the latest research on the role of ILCs in kidney disease.

ILCs are a newly identified subset of innate immune cells. They can provide early and rapid immune defence responses to protect epithelial cell integrity and maintain tissue immunity [1]. ILCs exhibit a typical lymphoid cell morphology but do not have rearranged antigen-specific receptors [2], [3], [4], [5]. Similar to T and B-lymphocytes, ILCs originate from common lymphoid progenitors (CLPs). CLPs differentiate into common innate lymphoid progenitors (CILPs), which serve as precursors for natural killer (NK) cells and ILCs. CILPs develop into common helper innate lymphoid progenitors (CHILPs), which are common precursors for lymphoid tissue inducer (LTi) cells and ILCs [6], [7]. CHILPs then differentiate into ILC precursors (ILCPs) or regulatory ILCs (ILCreg); ILCPs eventually produce ILC1s, ILC2s, and ILC3s (Fig. 1) [5], [8]. ILCs do not express T cell, B cell, or myeloid lineage markers (thus lineage-negative, Lin−), but express interleukin (IL)-2 receptors (CD25) and IL-7 receptors (IL7R or CD127). Although they share phenotypic and functional similarities with T cells, they are not identical [5], [9].

ILCs are primarily found in mucosal tissues, such as the intestine, lungs, and skin. They connect innate and adaptive immunity by regulating immune homeostasis through the secretion of various cytokines [2], [10]. ILCs are tissue-resident cells with a strong proliferative capacity during inflammation. Current studies emphasized the migration behaviors of ILCs [11], confirming inter-organ migration, for example, gut ILC2s migrate to the lungs and gut ILC3s migrate to draining mesenteric lymph nodes during infection. During blood glucose regulation, ILC2s actively migrate from the intestines to the pancreas, where they stimulate glucagon secretion by pancreatic α-cells through cytokines [12]. Furthermore, ILCs modulate the interactions between innate and adaptive immune cells, such as T cells [13], B cells [14], macrophages [15], and neutrophils [16], amplifying systemic or local immune responses by increasing antibody and cytokine production. These interactions may exacerbate disease progression [17]. For example, ILCs contribute to the development of chronic inflammatory diseases, including allergic reactions, inflammatory bowel disease (IBD), ulcerative colitis, asthma, and psoriasis [13], [18], [19]. They also contribute to autoimmune diseases, such as systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis [20]. Despite the close association between kidney diseases and the immune system, the role of ILCs in these conditions remains unclear.

This review presents recent advances in ILC research in the context of kidney disease to provide theoretical foundations and potential directions for clinically targeted therapies for kidney diseases.