0000000000939228
AUTHOR
Federica Macaluso
ILC3 in Axial Spondyloarthritis: the Gut Angle
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…
Pro-inflammatory CX3CR1+ CD59+ TL1A+ IL-23+ monocytes are expanded in patients with Ankylosing Spondylitis and modulate ILC3 immune functions
Gut derived ILC3 have been demonstrated to participate in AS pathogenesis. CX3CR1+ mononuclear phagocytes (MNP) have been demonstrated to modulate ILC3 function in the gut. The aim of this study was to study the role of pro-inflammatory CX3CR1+ CD59+ MNP in modulating ILC3 function in AS patients.
Reply to: Safety and efficacy of secukinumab treatment in a patient with ankylosing spondylitis and concomitant multiple sclerosis: A commentary
No abstract available
FRI0152 Inflammasomes activation occurs in the inflamed tissues of as patients and drives il-23 expression
Background A growing body of evidences indicate that the aberrant activation of innate immune systems, occurring in genetically predisposed patients, drives inflammatory processes in Ankylosing Spondylitis (AS).1 Objectives Aim of this study was to evaluate the activation and the functional relevance of inflammasome pathways in patients with AS. Methods Intestinal, synovial and bone marrow expression of inflammasome pathways, pyroptosis and IL-1b and IL-18 was evaluated in AS patients. Organic acid extraction was performed on ileal samples as previously described on.2 The expression of the metabolite-sensing receptors GPR43 and GPR109A involved in the regulation of the intestinal inflammaso…
The craniovertebral junction in rheumatoid arthritis: State of the art
Rheumatoid arthritis (RA) is a chronic inflammatory disorder, characterized by polyarticular inflammation causing progressive joint damage and disability. The mechanisms underlying its pathogenesis involve activation of innate and adaptive immunity, microvascular endothelial cell activation, and inflammatory infiltration of lymphocytes and monocytes into the synovium. Spinal involvement in RA is not typical; when it occurs, the main radiological features are (1) atlantoaxial subluxation (AAS), which is the most typical form of cervical spine involvement; (2) cranial settling—also known as basilar impression, atlantoaxial impaction or superior migration of the odontoid—which is the most seve…
Gut-derived CD8+ tissue-resident memory T cells are expanded in the peripheral blood and synovia of SpA patients
We read with interest the recently published paper from Qaiyum et al 1 demonstrating a novel integrin-expressing mature Crohn's disease (CD)8+ T cell population defined as CD49a+CD103+β7+CD29+ cells in the synovial fluids of ankylosing spondylitis (AS) patients. Although the authors did not analyse gut samples from AS patients, they speculate that these cells might be gut-derived cells. Interestingly, as stated by authors, the transcriptional and phenotypic signature of these cells is reminiscent of human tissue-resident memory T cells (TRM). TRM are a subset of cells important as the first line of defence from infection in mucosal tissues, never studied in spondyloarthritis (SpA).2 For cla…
THU0164 Subclinical atherosclerosis and cardiovascular events in italian patients with rheumatoid arthritis: results from multicenter girrcs (gruppo italiano di ricerca in reumatologia clinica e sperimentale) study
Background Several studies showed a close relationship between Rheumatoid Arthritis (RA) and accelerated atherosclerosis [1,2]. At the best of our knowledge, no such study has been carried out in a large Italian series. Objectives To investigate the prevalence of presence of subclinical atherosclerosis and history of cardio-cerebrovascular events (CVEs), in 1266 patients consecutively admitted to Rheumatology Units throughout the whole Italy. Methods From 01/01/2015 to 31/12/2015, 1266 consecutive patients admitted to GIRRCS centres, satisfying ACR/EULAR criteria for RA were investigated for: i. traditional cardiovascular risk factors: gender, age, smoking habit, cholesterol, triglycerides,…
Subclinical atherosclerosis and history of cardiovascular events in Italian patients with rheumatoid arthritis: Results from a cross-sectional, multicenter GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) study.
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Pathogenesis of primary Sjögren's syndrome beyond B lymphocytes
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder affecting exocrine glands of the body, prevalently lacrimal and salivary glands. The pSS pathogenesis has been thought to be B-cell-centric and several clinical trials have been carried out in order to clarify the therapeutic role of B-cell depletion in patients with pSS. Unfortunately, however, B-cell depletion with rituximab has failed in demonstrating any significant results in pSS patients. Besides the contribution of B cells in the pathogenesis of pSS, effector Tfh, Th17 and Th22 cells, follicular dendritic cells (DCs), innate cells (ICs) and several cytokines, chemokines and miRNA have been proved to participate to the …
Pathogenesis of polymyalgia rheumatica
Polymyalgia rheumatica (PMR) is a chronic, inflammatory disorder of unknown cause, almost exclusively occurring in people aged over 50 and often associated with giant cell arteritis. The evidence that PMR occurs almost exclusively in individuals aged over 50 may indicate that age-related immune alterations in genetically predisposed subjects contribute to development of the disease. Several infectious agents have been investigated as possible triggers of PMR even though the results are inconclusive. Activation of the innate and adaptive immune systems has been proved in PMR patients as demonstrated by the activation of dendritic cells and monocytes/macrophages and the altered balance betwee…
Proinflammatory CX3CR1+CD59+Tumor Necrosis Factor–Like Molecule 1A+Interleukin‐23+ Monocytes Are Expanded in Patients With Ankylosing Spondylitis and Modulate Innate Lymphoid Cell 3 Immune Functions
Objective: Gut-derived innate lymphoid cell 3 (ILC3) has been shown to participate in the pathogenesis of ankylosing spondylitis (AS). CX3CR1+ mononuclear phagocytes (MNPs) have been demonstrated to modulate ILC3 function in the gut. This study was undertaken to investigate the role of proinflammatory CX3CR1+CD59+ MNPs in modulating ILC3 function in AS patients. Methods: MNP subsets in the blood of AS patients and controls were analyzed by flow cytometry. The presence of CX3CR1+CD59+ cells in tissue was confirmed by confocal microscopy. Expression of the proinflammatory chemokines CX3CL1 and CCL2 and decoy receptor 6 (DcR-6) was analyzed. Peripheral CX3CR1+CD59+ cells were cocultured with I…
Histopathology of the gut in rheumatic diseases
The gastrointestinal tract regulates the trafficking of macromolecules between the environment and the host through an epithelial barrier mechanism and is an important part of the immune system controlling the equilibrium between tolerance and immunity to non-self-antigens. Various evidence indicates that intestinal inflammation occurs in patients with rheumatic diseases. In many rheumatic diseases intestinal inflammation appears to be linked to dysbiosis and possibly represents the common denominator in the pathogenesis of different rheumatic diseases. The continuative interaction between dysbiosis and the intestinal immune system may lead to the aberrant activation of immune cells that ca…