Emerging therapeutic potential of group 2 innate lymphoid cells in acute kidney injury

Abstract

Acute kidney injury (AKI) remains a global challenge and, despite the availability of dialysis and transplantation, can be fatal. Those that survive an AKI are at increased risk of developing chronic kidney disease and end stage renal failure. Understanding the fundamental mechanisms underpinning the pathophysiology of AKI is critical for developing novel strategies for diagnosis and treatment. A growing body of evidence indicates that amplifying type 2 immunity may have therapeutic potential in kidney injury and disease. Of particular interest are the recently described subset of innate immune cells, termed group 2 innate lymphoid cells (ILCs). Group 2 ILCs are crucial tissue‐resident immune cells that maintain homeostasis and regulate tissue repair at multiple organ sites, including the kidney. They are critical mediators of type 2 immune responses following infection and injury. The existing literature suggests that activation of group 2 ILCs and production of a local type 2 immune milieu is protective against renal injury and associated pathology. In this review, we describe the emerging role for group 2 ILCs in renal homeostasis and repair. We provide an in‐depth discussion of the most recent literature that use preclinical models of AKI and assess the therapeutic effect of modulating group 2 ILC function. We debate the potential for targeting these cells as novel cellular therapies in AKI and discuss the implications for future studies and translation. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Peritoneal M2 macrophage transplantation as a potential cell therapy for enhancing renal repair in acute kidney injury

“…The M2 phenotype can be induced ex vivo or in vivo via IL‐10 and transforming growth factor (TGF)‐β stimulation for treating kidney diseases . The type 2 innate lymphoid cells (ILC2s), which are a recently described innate immune cell population that can be activated by IL‐33 or IL‐25, also contribute to M2 polarization of macrophages through secretion of various type 2 cytokines, such as IL‐4 and IL‐13 …”

“…13 The type 2 innate lymphoid cells (ILC2s), which are a recently described innate immune cell population that can be activated by IL-33 or IL-25, also contribute to M2 polarization of macrophages through secretion of various type 2 cytokines, such as IL-4 and IL-13. [14][15][16] Recent studies have demonstrated that macrophages can be potentially used in cell therapies to induce immune tolerance to transplantation and to promote wound healing. 17,18 Cao Q et al 13,19 polarized the splenic macrophages to the M2 phenotype, which effectively reduced renal injury, by adoptive transfer of M2 macrophages to experimental models of adriamycin-induced kidney disease.…”

Regulation of Innate Lymphoid Cells in Acute Kidney Injury: Crosstalk between Cannabidiol and GILZ

“…This property likely contributes to the important roles of ILCs not only in immune responses against pathogens and sterile inflammation but also in maintaining tissue hemostasis. Nonetheless, differential development and activation of ILCs in a context-and/or disease-specific manner may contribute to inflammatory responses and/or outcome of treatment modalities [20][21][22][23][24][25][26][27].…”

Innate Lymphoid Cells in Renal Inflammation

“…Thus, immunomodulatory strategies that are aimed at shifting the balance from a pro-inflammatory, tissue destructive immune response in the kidney to an anti-inflammatory, pro-regenerative response are promising candidates for the development of novel therapies for kidney diseases. In this context, several recent studies identified kidney-residing Innate lymphoid cells (ILCs) as potential therapeutic targets in the attempt to promote tissue regeneration in AKI and/or slow progression of CKD (8).…”