Reduction of circulating innate lymphoid cell progenitors results in impaired cytokine production by innate lymphoid cells in patients with lupus nephritis
Open Access
- 29 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Arthritis Research & Therapy
- Vol. 22 (1), 1-13
- https://doi.org/10.1186/s13075-020-2114-5
Abstract
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). 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. 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. 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.Funding Information
- Korea Healthcare Technology R&D Project, Ministry of Health and Welfare (HI15C3083 and HI15C1736)
- National Research Foundation of Korea (SRC 2017R1A5A1014560)
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