Search results for "Interleukin 23"

Subclinical gut inflammation in ankylosing spondylitis

2015

Purpose of review Subclinical gut inflammation has been described in a significant proportion of patients with ankylosing spondylitis (AS), up to 10% of them developing it during the time of clinically overt inflammatory bowel disease. Histologic, immunologic, and intestinal microbiota alterations characterize the AS gut. Recent findings Microbial dysbiosis as well as alterations of innate immune responses have been demonstrated in the gut of AS. Furthermore, a growing body of evidence suggests that the gut of AS patients may be actively involved in the pathogenesis of AS through the production of proinflammatory cytokines, such as IL-23p19, and the differentiation of potentially pathogenic…

IL-17 polarization of MAIT cells is derived from the activation of two different pathways

2017

MAIT cells are expanded in salivary glands of patients with Sjogren's syndrome and are IL-17 polarized. IL-7 and IL-23 induce IL-17 production activating two different pathways: IL-7 stimulation induces in fact a significant STAT3 and HIF1alpha upregulation, conversely, IL-23 stimulation significantly induces RORc overexpression in MAIT cells of patients with Sjogren's syndrome.

ILC3 in Axial Spondyloarthritis: the Gut Angle

2019

Purpose of Review: A growing body of evidence supports the relevance of the interleukin-23/interleukin-17 (IL-23/IL-17) pathway for the pathogenesis of axial spondyloarthritis (axSpA) and its treatment. Recently, innate lymphoid cells (ILC), a heterogeneous family of immune effector cells, have been identified as a relevant contributor in tissue homeostasis, partially via IL-23/IL-17 axis. This review describes the biology and the origins of the group 3 ILCs (ILC3s) in humans, focusing on their role in the pathogenesis of axSpA. Recent Findings: Clinical trials showed the effectiveness of IL23/IL-17 axis inhibition in both spondyloarthritis (SpA) and Inflammatory Bowel Disease (IBD). Recent…

Inflammasome activation in Ankylosing Spondylitis is associated to gut dysbiosis

2021

Objective: We undertook this study to evaluate the activation and functional relevance of inflammasome pathways in ankylosing spondylitis (AS) patients and rodent models and their relationship to dysbiosis. Methods: An inflammasome pathway was evaluated in the gut and peripheral blood from 40 AS patients using quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), flow cytometry, and confocal microscopy, and was compared to that of 20 healthy controls and 10 patients with Crohn’s disease. Bacteria was visualized using silver stain in human samples, and antibiotics were administered to HLA–B27–transgenic rats. The NLRP3 inhibitor MCC950 was admini…

Fate-Mapping of GM-CSF Expression Identifies a Discrete Subset of Inflammation-Driving T Helper Cells Regulated by Cytokines IL-23 and IL-1β.

2019

Summary Pathogenic lymphocytes initiate the development of chronic inflammatory diseases. The cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) (encoded by Csf2) is a key communicator between pathogenic lymphocytes and tissue-invading inflammatory phagocytes. However, the molecular properties of GM-CSF-producing cells and the mode of Csf2 regulation in vivo remain unclear. To systematically study and manipulate GM-CSF+ cells and their progeny in vivo, we generated a fate-map and reporter of GM-CSF expression mouse strain (FROG). We mapped the phenotypic and functional profile of auto-aggressive T helper (Th) cells during neuroinflammation and identified the signature and pa…

Parasite Clearance in Leishmaniasis in Resistant Animals Is Independent of the IL-23/IL-17A Axis

2015

Intestinal dysbiosis and innate immune responses in axial spondyloarthritis

2016

Purpose of review Inflammatory innate and adaptive immune cell responses to commensal bacteria underlie the pathogenesis of human chronic inflammatory diseases. Intestinal dysbiosis has been described in patients with spondyloarthritis (SpA) and seems to be correlated with histologic and immunologic alterations. Purpose of this review is to discuss the relationship occurring between intestinal dysbiosis and innate immune responses in patients with axial SpA. Recent findings Intestinal dysbiosis and differential activation of intestinal immune responses in patients with SpA have been demonstrated. Furthermore, innate cells that appear to be involved in the pathogenesis of SpA may control int…

Nutritional control of IL-23/Th17-mediated autoimmune disease through HO-1/STAT3 activation

2017

AbstractThe nutritional curcumin (CUR) is beneficial in cell-mediated autoimmune diseases. The molecular mechanisms underlying this food-mediated silencing of inflammatory immune responses are poorly understood. By investigating antigen-specific immune responses we found that dietary CUR impairs the differentiation of Th1/Th17 cells in vivo during encephalomyelitis and instead promoted Th2 cells. In contrast, feeding CUR had no inhibitory effect on ovalbumin-induced airway inflammation. Mechanistically, we found that CUR induces an anti-inflammatory phenotype in dendritic cells (DC) with enhanced STAT3 phosphorylation and suppressed expression of Il12b and Il23a. On the molecular level CUR …

Monocyte-derived inflammatory Langerhans cells and dermal dendritic cells mediate psoriasis-like inflammation

2016

Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined. Here we show that DCs are required for psoriasis-like changes in mouse skin induced by the local injection of IL-23. However, Flt3L-dependent DCs and resident Langerhans cells are dispensable for the inflammation. In epidermis and dermis, the critical DCs are TNF-producing and IL-1β-producing monocyte-derived DCs, including a population of inflammatory Langerhans cells. Depleting Ly6Chi blood monocytes reduces DC accumulation and the skin changes induced either by injecting IL-23 or by application of the TLR7 agonist imiquimod. Moreover, we find that IL-23-…

Insufficient generation of Th17 cells in IL-23p19-deficient BALB/c mice protects against progressive cutaneous leishmaniasis

2017

Healing of leishmaniasis-a parasitic skin disease-is associated with high levels of secreted interferon (IFN)γ and IL-12 in resistant C57BL/6 mice and humans. Susceptible BALB/c mice predominantly react with a Th17/Th2/Treg-related immune response and finally succumb to infection. Previously, we showed that BALB/c IL-17A-/- mice are protected against Leishmania (L.) major infections, indicating that IL-17A-predominantly produced by Th17 cells-plays an important role for disease outcome. We now investigated DC-derived cytokines and finally identified IL-23p19 as key cytokine responsible for induction of Leishmania-specific Th17 cells that play an important role for progressive disease in sus…