Lymphocytes: Versatile Participants in Acute Kidney Injury and Progression to Chronic Kidney Disease.

Chujin Cao,Rui Zeng,Ying Yao

doi:10.3389/fphys.2021.729084

Chujin Cao, Rui Zeng + Show 1 more

Open Access

https://doi.org/10.3389/fphys.2021.729084

Copy DOI

Abstract

Background: Acute kidney injury (AKI) remains a major global public health concern due to its high morbidity and mortality. The progression from AKI to chronic kidney disease (CKD) makes it a scientific problem to be solved. However, it is with lack of effective treatments.Summary: Both innate and adaptive immune systems participate in the inflammatory process during AKI, and excessive or dysregulated immune responses play a pathogenic role in renal fibrosis, which is an important hallmark of CKD. Studies on the pathogenesis of AKI and CKD have clarified that renal injury induces the production of various chemokines by renal parenchyma cells or resident immune cells, which recruits multiple-subtype lymphocytes in circulation. Some infiltrated lymphocytes exacerbate injury by proinflammatory cytokine production, cytotoxicity, and interaction with renal resident cells, which constructs the inflammatory environment and induces further injury, even death of renal parenchyma cells. Others promote tissue repair by producing protective cytokines. In this review, we outline the diversity of these lymphocytes and their mechanisms to regulate the whole pathogenic stages of AKI and CKD; discuss the chronological responses and the plasticity of lymphocytes related to AKI and CKD progression; and introduce the potential therapies targeting lymphocytes of AKI and CKD, including the interventions of chemokines, cytokines, and lymphocyte frequency regulation in vivo, adaptive transfer of ex-expanded lymphocytes, and the treatments of gut microbiota or metabolite regulations based on gut-kidney axis.Key Message: In the process of AKI and CKD, T helper (Th) cells, innate, and innate-like lymphocytes exert mainly pathogenic roles, while double-negative T (DNT) cells and regulatory T cells (Tregs) are confirmed to be protective. Understanding the mechanisms by which lymphocytes mediate renal injury and renal fibrosis is necessary to promote the development of specific therapeutic strategies to protect from AKI and prevent the progression of CKD.

Highlights

Despite the identification of clinical diagnosis and application of dialysis, acute kidney injury (AKI) remains a major global public health concern due to high morbidity and mortality with few systematic efforts to manage it including prevention, diagnosis, and treatments (Mehta et al, 2015)
We summarized the mechanisms by which various types of lymphocytes participate in AKI, subsequent repair and progression to chronic kidney disease (CKD) with a focus on T cells and innate lymphoid cells (ILCs)
The diversity and plasticity of lymphocytes result in their multifunction for renal injury and fibrosis

Summary

Background

Acute kidney injury (AKI) remains a major global public health concern due to its high morbidity and mortality. The progression from AKI to chronic kidney disease (CKD) makes it a scientific problem to be solved. It is with lack of effective treatments. Summary: Both innate and adaptive immune systems participate in the inflammatory process during AKI, and excessive or dysregulated immune responses play a pathogenic role in renal fibrosis, which is an important hallmark of CKD. Studies on the pathogenesis of AKI and CKD have clarified that renal injury induces the production of various chemokines by renal parenchyma cells or resident immune cells, which recruits multiple-subtype lymphocytes in circulation.

INTRODUCTION

Findings

CONCLUSIONS