Review: Innate Lymphoid Cells: Sparking Inflammatory Rheumatic Disease?

Wenink, Mark H.; Leijten, Emmerik F A; Cupedo, Tom

doi:10.1002/art.40068

Cited by 14 publications

(7 citation statements)

References 114 publications

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“…Although ILCs play roles in several autoimmune diseases, including rheumatoid arthritis, juvenile inflammatory arthritis, spondyloarthritis, and systemic sclerosis [11][12][13][14], their role in autoimmune kidney diseases is unclear. Recently, ILC2s were identified as a major ILC population in the healthy kidneys of mice [15].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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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Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…When dysregulated, these tissue‐resident immune cells have been shown to participate in the pathogenesis and tissue injury in autoimmune diseases . Evidence for a role of ILCs in joint inflammation has been revealed in rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis . The results from clinical studies have suggested that the ILCs in the joint appear to act as critical effector cells and contribute to the pathogenesis through both IFN‐γ secretion (ILC‐1‐like activity) and IL‐17A, IL‐22 and TNF‐α production (ILC‐3‐like activity) .…”

Section: Discussionmentioning

confidence: 99%

“…ILCs have been studied in the mucosa and the serosa and were shown to play important roles in immune responses to maintain tissue homeostasis through crosstalk with many other cell types . Meanwhile, their dysregulation has been found to have a pathogenic role in autoimmune diseases . Different from T cells, ILCs appear to be particularly sensitive to cues from tissue factors (including cytokines) for cell reprogramming .…”

Section: Introductionmentioning

confidence: 99%

Increased ILC3s associated with higher levels of IL‐1β aggravates inflammatory arthritis in mice lacking phagocytic NADPH oxidase

et al. 2019

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The role of redox regulation in immune-mediated arthritis has been previously described. However, the relationship between innate immune cells, including innate lymphoid cells (ILCs) and phagocyte-derived ROS, in this process remains unclear. Here, we characterize ILCs and measure the IL-1 family cytokines along with other cytokines relevant to ILC functions and development in serum-induced arthritic joints in wild type and phagocytic NADPH oxidase (NOX2)-deficient Ncf1 −/− mice. We found more severe serum-induced joint inflammation and increased NCR + ILC3s in inflamed joints of Ncf1 −/− mice. Furthermore, in vitro stimulation with IL-1β on Tbet + ILC1s from joints facilitated their differentiation into ROR-γt + ILC3s. Moreover, treatment with IL-1 antagonists effectively lowered the proportions of NCR + ILC3s and IL-17A producing ILC3s in Ncf1 −/− arthritic mice and ameliorated the joint inflammation. These results suggest that NOX2 is an essential reg- ulator of ILC transdifferentiation and may mediate this process in a redox-dependent manner through IL-1β production in the inflammatory joint. Our findings shed important light on the role of ILCs in the initiation and progression in tissue inflammation and delineate a novel innate immune cell-mediated pathogenic mechanism through which redox regulation may determine the direction of immune responses in joints.Keywords: chronic granulomatous disease r innate lymphoid cells r NADPH oxidase r reactive oxygen species r serum-induced arthritis Additional supporting information may be found online in the Supporting Information section at the end of the article.

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“…Aspects that deserve to be clarified are mainly related to the migration of ILC3 in salivary gland tissues, their role in forming TLS and their interaction with epithelial cells [104]. Specifically, ILCs express the NKp30 receptor on their surface, the same receptor can be found on NK cells.…”

Section: Innate Lymphoid Cells (Ilcs)mentioning

confidence: 99%

Primary Sjogren Syndrome: Focus on Innate Immune Cells and Inflammation

et al. 2020

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Primary Sjogren Syndrome (pSS) is a complex, multifactorial rheumatic disease that mainly targets salivary and lacrimal glands, inducing epithelitis. The cause behind the autoimmunity outbreak in pSS is still elusive; however, it seems related to an aberrant reaction to exogenous triggers such as viruses, combined with individual genetic pre-disposition. For a long time, autoantibodies were considered as the hallmarks of this disease; however, more recently the complex interplay between innate and adaptive immunity as well as the consequent inflammatory process have emerged as the main mechanisms of pSS pathogenesis. The present review will focus on innate cells and on the principal mechanisms of inflammation connected. In the first part, an overview of innate cells involved in pSS pathogenesis is provided, stressing in particular the role of Innate Lymphoid Cells (ILCs). Subsequently we have highlighted the main inflammatory pathways, including intra- and extra-cellular players. A better knowledge of such processes could determine the detection of new therapeutic targets that are a major need for pSS.

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Review: Innate Lymphoid Cells: Sparking Inflammatory Rheumatic Disease?

Cited by 14 publications

References 114 publications

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

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

Increased ILC3s associated with higher levels of IL‐1β aggravates inflammatory arthritis in mice lacking phagocytic NADPH oxidase

Primary Sjogren Syndrome: Focus on Innate Immune Cells and Inflammation

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