Innate Lymphoid Cells in Autoimmune Diseases

Clottu, Aurélie; Humbel, Morgane; Fluder, Natalia; Karampetsou, Maria P.; Comte, Denis

doi:10.3389/fimmu.2021.789788

Cited by 35 publications

(25 citation statements)

References 76 publications

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“…ILCs are involved in maintaining the integrity of the epithelium and homeostasis, tissue repair, and rapid response against pathogens. The role of these different ILC subpopulations in MG should be investigated in detail as their implication in autoimmunity is beginning to emerge ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Single-cell mass cytometry on peripheral cells in Myasthenia Gravis identifies dysregulation of innate immune cells

et al. 2023

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Myasthenia Gravis (MG) is a neurological autoimmune disease characterized by disabling muscle weaknesses due to anti-acetylcholine receptor (AChR) autoantibodies. To gain insight into immune dysregulation underlying early-onset AChR+ MG, we performed an in-depth analysis of peripheral mononuclear blood cells (PBMCs) using mass cytometry. PBMCs from 24 AChR+ MG patients without thymoma and 16 controls were stained with a panel of 37 antibodies. Using both unsupervised and supervised approaches, we observed a decrease in monocytes, for all subpopulations: classical, intermediate, and non-classical monocytes. In contrast, an increase in innate lymphoid cells 2 (ILC2s) and CD27- γδ T cells was observed. We further investigated the dysregulations affecting monocytes and γδ T cells in MG. We analyzed CD27- γδ T cells in PBMCs and thymic cells from AChR+ MG patients. We detected the increase in CD27- γδ T cells in thymic cells of MG patients suggesting that the inflammatory thymic environment might affect γδ T cell differentiation. To better understand changes that might affect monocytes, we analyzed RNA sequencing data from CD14+ PBMCs and showed a global decrease activity of monocytes in MG patients. Next, by flow cytometry, we especially confirmed the decrease affecting non-classical monocytes. In MG, as for other B-cell mediated autoimmune diseases, dysregulations are well known for adaptive immune cells, such as B and T cells. Here, using single-cell mass cytometry, we unraveled unexpected dysregulations for innate immune cells. If these cells are known to be crucial for host defense, our results demonstrated that they could also be involved in autoimmunity.

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Section: Discussionmentioning

confidence: 99%

Single-cell mass cytometry on peripheral cells in Myasthenia Gravis identifies dysregulation of innate immune cells

et al. 2023

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“…Indeed, ILC3 seem to be involved in AS pathogenesis from several pieces of evidence. These cells are located mainly at mucosal barriers, in particular in the gut where they regulate interactions with the microbiome and gut homeostasis [ 78 , 79 ]. Two distinct ILC3 populations including NKp44 + and NKp44 - cells may be recognised.…”

Section: Role Of Innate Immunitymentioning

confidence: 99%

Uncovering the Underworld of Axial Spondyloarthritis

Vescovo

Venerito

Iannone

et al. 2023

IJMS

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Axial spondyloarthritis (axial-SpA) is a multifactorial disease characterized by inflammation in sacroiliac joints and spine, bone reabsorption, and aberrant bone deposition, which may lead to ankylosis. Disease pathogenesis depends on genetic, immunological, mechanical, and bioenvironmental factors. HLA-B27 represents the most important genetic factor, although the disease may also develop in its absence. This MHC class I molecule has been deeply studied from a molecular point of view. Different theories, including the arthritogenic peptide, the unfolded protein response, and HLA-B27 homodimers formation, have been proposed to explain its role. From an immunological point of view, a complex interplay between the innate and adaptive immune system is involved in disease onset. Unlike other systemic autoimmune diseases, the innate immune system in axial-SpA has a crucial role marked by abnormal activity of innate immune cells, including γδ T cells, type 3 innate lymphoid cells, neutrophils, and mucosal-associated invariant T cells, at tissue-specific sites prone to the disease. On the other hand, a T cell adaptive response would seem involved in axial-SpA pathogenesis as emphasized by several studies focusing on TCR low clonal heterogeneity and clonal expansions as well as an interindividual sharing of CD4/8 T cell receptors. As a result of this immune dysregulation, several proinflammatory molecules are produced following the activation of tangled intracellular pathways involved in pathomechanisms of axial-SpA. This review aims to expand the current understanding of axial-SpA pathogenesis, pointing out novel molecular mechanisms leading to disease development and to further investigate potential therapeutic targets.

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“…Über Zytokinproduktion, insbesondere auch IL-5, kann eine Th2-Immunantwort initiiert sowie Eosinophile und Mastzellen rekrutiert werden. Eine potentielle Rolle von ILCs in der Pathophysiologie der EGPA bleibt noch unklar, allerdings erscheint eine Vermittlungsfunktion zwischen angeborenem und erworbenem Immunsystem möglich [7].…”

Section: Pathophysiologieunclassified

Eosinophile Granulomatose mit Polyangiitis – ein Übersichtsartikel

Schindler

Venhoff

2022

Aktuelle Rheumatologie

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ZusammenfassungDie eosinophile Granulomatose mit Polyangiitis (EGPA) ist eine seltene Form der ANCA-assoziierten Vaskulitiden (AAV) aus der Gruppe der Kleingefäßvaskulitiden. Sie ist definiert als eine Vaskulitis kleiner und mittelgroßer Gefäße mit granulomatöser Entzündung sowie Blut- und Gewebseosinophilie. Fast alle Patienten haben allergische Symptome mit Asthma bronchiale und rhinosinusitischen Beschwerden. Das sonstige klinische Spektrum variiert je nach Lokalisation, Schweregrad und Art der Krankheitsmanifestation. Durch die eosinophile Infiltration und Inflammation kann es zu Rhinosinusitis, Pneumonitis, gastrointestinaler Beteiligung und Kardiomyopathie kommen. Insbesondere Letztere ist mit einer schlechteren Prognose assoziiert. Als nekrotisierende pauci-immune Kleingefäßvaskulitis kann die EGPA, ähnlich wie die anderen AAV, pulmonale Infiltrate mit alveolärer Hämorrhagie, eine Glomerulonephritis, kutane Vaskulitis mit Purpura, sowie zentrale und periphere neurologische Schädigungen verursachen. Das Auftreten perinukleärer ANCA (pANCA), mit Spezifität gegen die Myeloperoxidase (MPO) wird in etwa einem Drittel der Fälle beobachtet, ist allerdings nicht spezifisch für die EGPA. MPO-ANCA-positive Patienten haben häufiger eine periphere neurologische Beteiligung und eine Glomerulonephritis, während ANCA-negative Patienten häufiger eine kardiale und pulmonale Beteiligung aufweisen. Eine differentialdiagnostische Herausforderung im klinischen Alltag stellt die Abgrenzung zum hypereosinophilen Syndrom (HES) dar. Das Therapiekonzept der EGPA hängt davon ab, ob der Schweregrad der Erkrankung potentiell Organ- oder lebensbedrohlich ist. Bei schweren Formen der EGPA werden in der Akuttherapie hauptsächlich Glukokortikoide in Kombination mit Cyclophosphamid eingesetzt. Rituximab wird mittlerweile als alternative Behandlungsoption in den Leitlinien genannt. Zur Remissionserhaltung stehen verschiedene immunsuppressive Therapien zur Verfügung. Bei EGPA ohne schwere Organbeteiligung ist die IL-5 Blockade mit Mepolizumab zugelassen.

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Innate Lymphoid Cells in Autoimmune Diseases

Cited by 35 publications

References 76 publications

Single-cell mass cytometry on peripheral cells in Myasthenia Gravis identifies dysregulation of innate immune cells

Single-cell mass cytometry on peripheral cells in Myasthenia Gravis identifies dysregulation of innate immune cells

Uncovering the Underworld of Axial Spondyloarthritis

Eosinophile Granulomatose mit Polyangiitis – ein Übersichtsartikel

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