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

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 a...

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Main Authors: Chujin Cao, Ying Yao, Rui Zeng
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-09-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2021.729084/full
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author Chujin Cao
Ying Yao
Rui Zeng
author_facet Chujin Cao
Ying Yao
Rui Zeng
author_sort Chujin Cao
collection DOAJ
description 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.
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spelling doaj.art-ccc21bed694449fc8ab7dfa43923dfa12022-12-21T23:24:49ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-09-011210.3389/fphys.2021.729084729084Lymphocytes: Versatile Participants in Acute Kidney Injury and Progression to Chronic Kidney DiseaseChujin CaoYing YaoRui ZengBackground: 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.https://www.frontiersin.org/articles/10.3389/fphys.2021.729084/fulllymphocytesacute kidney injurytubular cell damagerenal fibrosischronic kidney diseasegut microbiota
spellingShingle Chujin Cao
Ying Yao
Rui Zeng
Lymphocytes: Versatile Participants in Acute Kidney Injury and Progression to Chronic Kidney Disease
Frontiers in Physiology
lymphocytes
acute kidney injury
tubular cell damage
renal fibrosis
chronic kidney disease
gut microbiota
title Lymphocytes: Versatile Participants in Acute Kidney Injury and Progression to Chronic Kidney Disease
title_full Lymphocytes: Versatile Participants in Acute Kidney Injury and Progression to Chronic Kidney Disease
title_fullStr Lymphocytes: Versatile Participants in Acute Kidney Injury and Progression to Chronic Kidney Disease
title_full_unstemmed Lymphocytes: Versatile Participants in Acute Kidney Injury and Progression to Chronic Kidney Disease
title_short Lymphocytes: Versatile Participants in Acute Kidney Injury and Progression to Chronic Kidney Disease
title_sort lymphocytes versatile participants in acute kidney injury and progression to chronic kidney disease
topic lymphocytes
acute kidney injury
tubular cell damage
renal fibrosis
chronic kidney disease
gut microbiota
url https://www.frontiersin.org/articles/10.3389/fphys.2021.729084/full
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AT yingyao lymphocytesversatileparticipantsinacutekidneyinjuryandprogressiontochronickidneydisease
AT ruizeng lymphocytesversatileparticipantsinacutekidneyinjuryandprogressiontochronickidneydisease