Reduction of circulating innate lymphoid cell progenitors results in impaired cytokine production by innate lymphoid cells in patients with lupus nephritis

Abstract Background Innate lymphoid cells (ILCs) play an essential role in maintaining homeostasis; however, they can also cause chronic inflammation and autoimmune disease. This study aimed to identify the role of ILCs in the pathogenesis of lupus nephritis (LN). Methods The percentage of ILCs with...

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Main Authors: Seungwon Ryu, Eun Young Lee, Dong Ki Kim, Yon Su Kim, Doo Hyun Chung, Ji Hyung Kim, Hajeong Lee, Hye Young Kim
Format: Article
Language:English
Published: BMC 2020-03-01
Series:Arthritis Research & Therapy
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13075-020-2114-5
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author Seungwon Ryu
Eun Young Lee
Dong Ki Kim
Yon Su Kim
Doo Hyun Chung
Ji Hyung Kim
Hajeong Lee
Hye Young Kim
author_facet Seungwon Ryu
Eun Young Lee
Dong Ki Kim
Yon Su Kim
Doo Hyun Chung
Ji Hyung Kim
Hajeong Lee
Hye Young Kim
author_sort Seungwon Ryu
collection DOAJ
description Abstract Background Innate lymphoid cells (ILCs) play an essential role in maintaining homeostasis; however, they can also cause chronic inflammation and autoimmune disease. This study aimed to identify the role of ILCs in the pathogenesis of lupus nephritis (LN). Methods The percentage of ILCs within the peripheral blood mononuclear cell (PBMC) population and urine of patients with LN (n = 16), healthy controls (HC; n = 8), and disease controls (ANCA-associated vasculitis (AAV; n = 6), IgA nephropathy (IgAN; n = 9), and other glomerular diseases (n = 5)) was determined by flow cytometry analysis. In addition, ILCs were sorted and cultured with plasma from LN patients or HC to elucidate whether the reduced population of CD117+ ILCs observed in LN was due to changes in the ILC progenitor population. Results The percentage of total ILCs and CD117+ ILCs in LN was significantly lower than that in HC. The percentage of cytokine-secreting ILCs was also lower in LN; however, when the disease stabilized, cytokine production was restored to levels similar to those in HC. The increase in the number of exhausted ILCs (cells unable to secrete cytokines) correlated positively with disease activity. When CD117+ ILCs were cultured with LN plasma, the number of CD117+ ILCs fell, but that of other ILC subsets increased. Conclusions The percentage of CD117+ ILCs and the capacity of ILCs to secrete cytokines fell as LN severity increased, suggesting that an inflammatory environment of LN induces persistent differentiation and exhaustion of ILCs.
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spelling doaj.art-b862ec52ffda4f71a37c82ad31d9248a2022-12-21T21:10:05ZengBMCArthritis Research & Therapy1478-63622020-03-0122111310.1186/s13075-020-2114-5Reduction of circulating innate lymphoid cell progenitors results in impaired cytokine production by innate lymphoid cells in patients with lupus nephritisSeungwon Ryu0Eun Young Lee1Dong Ki Kim2Yon Su Kim3Doo Hyun Chung4Ji Hyung Kim5Hajeong Lee6Hye Young Kim7Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of MedicineDivision of Rheumatology, Department of Internal Medicine, Seoul National University HospitalDivision of Nephrology, Department of Internal Medicine, Seoul National University HospitalDivision of Nephrology, Department of Internal Medicine, Seoul National University HospitalDepartment of Pathology, Seoul National University College of MedicineCollege of Life Sciences and Biotechnology, Korea UniversityDivision of Nephrology, Department of Internal Medicine, Seoul National University HospitalLaboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of MedicineAbstract Background Innate lymphoid cells (ILCs) play an essential role in maintaining homeostasis; however, they can also cause chronic inflammation and autoimmune disease. This study aimed to identify the role of ILCs in the pathogenesis of lupus nephritis (LN). Methods The percentage of ILCs within the peripheral blood mononuclear cell (PBMC) population and urine of patients with LN (n = 16), healthy controls (HC; n = 8), and disease controls (ANCA-associated vasculitis (AAV; n = 6), IgA nephropathy (IgAN; n = 9), and other glomerular diseases (n = 5)) was determined by flow cytometry analysis. In addition, ILCs were sorted and cultured with plasma from LN patients or HC to elucidate whether the reduced population of CD117+ ILCs observed in LN was due to changes in the ILC progenitor population. Results The percentage of total ILCs and CD117+ ILCs in LN was significantly lower than that in HC. The percentage of cytokine-secreting ILCs was also lower in LN; however, when the disease stabilized, cytokine production was restored to levels similar to those in HC. The increase in the number of exhausted ILCs (cells unable to secrete cytokines) correlated positively with disease activity. When CD117+ ILCs were cultured with LN plasma, the number of CD117+ ILCs fell, but that of other ILC subsets increased. Conclusions The percentage of CD117+ ILCs and the capacity of ILCs to secrete cytokines fell as LN severity increased, suggesting that an inflammatory environment of LN induces persistent differentiation and exhaustion of ILCs.http://link.springer.com/article/10.1186/s13075-020-2114-5Lupus nephritisAutoimmune kidney diseaseInnate lymphoid cells (ILCs)Cytokine
spellingShingle Seungwon Ryu
Eun Young Lee
Dong Ki Kim
Yon Su Kim
Doo Hyun Chung
Ji Hyung Kim
Hajeong Lee
Hye Young Kim
Reduction of circulating innate lymphoid cell progenitors results in impaired cytokine production by innate lymphoid cells in patients with lupus nephritis
Arthritis Research & Therapy
Lupus nephritis
Autoimmune kidney disease
Innate lymphoid cells (ILCs)
Cytokine
title Reduction of circulating innate lymphoid cell progenitors results in impaired cytokine production by innate lymphoid cells in patients with lupus nephritis
title_full Reduction of circulating innate lymphoid cell progenitors results in impaired cytokine production by innate lymphoid cells in patients with lupus nephritis
title_fullStr Reduction of circulating innate lymphoid cell progenitors results in impaired cytokine production by innate lymphoid cells in patients with lupus nephritis
title_full_unstemmed Reduction of circulating innate lymphoid cell progenitors results in impaired cytokine production by innate lymphoid cells in patients with lupus nephritis
title_short Reduction of circulating innate lymphoid cell progenitors results in impaired cytokine production by innate lymphoid cells in patients with lupus nephritis
title_sort reduction of circulating innate lymphoid cell progenitors results in impaired cytokine production by innate lymphoid cells in patients with lupus nephritis
topic Lupus nephritis
Autoimmune kidney disease
Innate lymphoid cells (ILCs)
Cytokine
url http://link.springer.com/article/10.1186/s13075-020-2114-5
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