Checkpoint agonists - immunoregulatory role and its implications in the treatment of psoriasis and psoriatic arthritis.

Psoriasis and psoriatic arthritis are chronic autoimmune diseases characterized by dysregulated immune responses, particularly involving Th17 cells. Immune checkpoint molecules such as programmed death-1 (PD-1) and its ligands (PD-L1/PD-L2) are critical for maintaining immune tolerance. Disruptions in these pathways contribute to psoriatic disease pathogenesis.

Moving beyond the Janus kinase signaling kinases in the pathogenesis and treatment of psoriasis and psoriatic arthritis.

Psoriatic disease encompasses psoriasis and psoriatic arthritis. It is a chronic, progressive condition and leads to irreversible joint destruction. Conventional treatments used are disease-modifying antirheumatic drugs and biologics.

Total-body positron emission tomography: a tool for systemic, quantitative evaluation of the inflammatory burden of psoriatic arthritis.

Objectives: To test the hypothesis that recently-developed total body-positron emission tomography (TB-PET) imaging with integrated computed tomography (CT) will enable low-dose, quantitative, domain-specific evaluation of the total inflammatory burden of psoriatic arthritis (PsA) and associate with established outcome measures of the clinical domains of PsA.

Methods: Seventy-one adult participants (40 with PsA, 16 with rheumatoid arthritis (RA), and 15 with osteoarthritis (OA)) underwent 20-min TB-PET/CT scans using [18F]FDG, a glucose analogue radiotracer. [18F]FDG uptake was assessed qualitatively and quantitatively.

GRAPPA 2023 Basic Science Workshop: What to Expect From Animal Models for Psoriatic Arthritis and Psoriasis.

Animal models help to drive research into psoriasis and psoriatic arthritis (PsA), particularly when studies in humans are not feasible. There are no animal models that perfectly mimic psoriatic disease (PsD) and so the pros and cons of each existing model must be considered for appropriate experimental design. Roughly, the existing animal models for PsD can be divided into 4 categories: (1) spontaneous models, (2) transgenic models, (3) inducible models, and (4) xenotransplantation models.

JAK-STAT Signaling and Beyond in the Pathogenesis of Spondyloarthritis and Their Clinical Significance.

Purpose Of Review: Janus kinase-signal transducers and activators of transcription cell signaling proteins (JAK-STATs) play a key regulatory role in functioning of several inflammatory cytokines. JAK-STAT signaling proteins are the key regulators of the cytokine/cytokine receptor system involved in the pathogenesis of various autoimmune disease including spondyloarthritis (SpA). This article mainly highlights the JAK-STAT signaling system, its association with the relevant cytokine/cytokine-receptor system, and its regulatory role in pathogenesis of SpA.

JAK inhibitor: Introduction.

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is a key regulatory signaling system for cellular proliferation, differentiation, and apoptosis. In addition, JAK signaling pathway plays critical roles in orchestrating immune response through its interactions with the cytokine receptors and the transcriptions factors. Several key cytokines use JAK-STAT signaling proteins to transduce intra-cellular signals which are involved in the pathogenesis of autoimmune and inflammatory diseases such as in psoriatic disease (psoriasis, psoriatic arthritis), atopic dermatitis, alopecia areata, vitiligo, rheumatoid arthritis, ankylosing spondylitis, lupus erythematosus, Sjogren's syndrome, and other autoimmune diseases.

Janus kinase inhibitors for the treatment of psoriatic arthritis.

Psoriatic arthritis (PsA), a systemic disease, has multi-domain musculoskeletal pathologies along with dermatological manifestations. The current recommendations and the standard of care for the treatment of PsA is to address the domain-based pathologies and the disease severity of the six clinical domains unique to PsA, namely, arthritis of the large and small joints, skin involvement, nail involvement enthesitis, dactylitis and axial disease. With currently available therapies, there are good numbers of primary/secondary non-responders and there are added concerns because of intolerance and adverse effects.

JAK-STAT inhibitors in Immune mediated diseases: An Overview.

For any biological response, transmission of extracellular signals to the nucleus is required for DNA transcription and gene expression. In that respect, cytokines/chemokines are well-known inflammatory agents which play a critical role in signalling pathways by activating the Janus kinase-signal transducers and activators of transcription (JAK-STAT) signalling proteins (Janus kinase-signal transducers and activators of transcription) which are a group of intracellular kinase molecules. Cytokines are a category of small proteins (∼5-25 kDa) that play a major role in cell signalling and are major drivers of an autoimmune response.

Phenotype and pathological significance of MCAM (CD146) T cell subset in psoriatic arthritis.

Background: CD146 (MCAM-melanoma cell adhesion molecule) is a cell surface adhesion molecule for Laminin 411. T cells expressing MCAM are mainly responsible for IL-17 production. IL-17 secreting T helper cells (Th17 cells) are critical for the pathogenesis of psoriatic arthritis (PsA).

Targeting the CCR6/CCL20 Axis in Entheseal and Cutaneous Inflammation.

Objective: To assess the involvement of the CCR6/CCL20 axis in psoriatic arthritis (PsA) and psoriasis (PsO) and to evaluate its potential as a therapeutic target.

Methods: First, we quantified CCL20 levels in peripheral blood and synovial fluid from PsA patients and examined the presence of CCR6+ cells in synovial and tendon tissue. Utilizing an interleukin-23 minicircle DNA (IL-23 MC) mouse model exhibiting key features of both PsO and PsA, we investigated CCR6 and CCL20 expression as well as the preventive and therapeutic effect of CCL20 blockade.

Janus kinase-signal transducers and activators of transcription cell signaling in Spondyloarthritis: rationale and evidence for JAK inhibition.

Purpose Of Review: The Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling proteins represent a group of intracellular kinase molecules that play a central role in the signaling pathways induced by cytokines, chemokines, and certain growth factors associated with systemic and local inflammation of autoimmune diseases including in Spondyloarthritis (SpA). Here, we will discuss (i) the functional significance of the JAK-STAT kinase cascades in the inflammatory-proliferative processes of SpA and its cellular/molecular mechanisms (ii) progress in the development of oral synthetic JAK inhibitors (JAKi) and their therapeutic efficacies in SpA.

Recent Findings: Development JAKi is a fast-moving field in the medical science.

Updated therapies for the management of Psoriatic Arthritis.

Psoriatic arthritis (PsA) is a large volume of our clinical practice and its management can be challenging. Traditional DMARDs have been used over last six decades and observational studies have substantiated an effective use of many of these drugs. However, in last two decades use of anti-TNF agents has brought a new dimension in treatment of PsA and in many other autoimmune diseases.

Risk of tuberculosis with anti-tumor necrosis factor-alpha therapy in patients with psoriasis and psoriatic arthritis in Indian population.

Anti-tumor necrosis factor-alpha (TNF-α) immunotherapy has revolutionized the treatment of inflammatory diseases, such as psoriasis and psoriatic arthritis. However, a major concern is that patients receiving this therapy have an increased risk of infection, particularly of reactivation of latent tuberculosis (TB). There were an estimated 10.

Functional significance of MAIT cells in psoriatic arthritis.

Background: Mucosal-associated invariant T (MAIT) cells are gaining more relevance for autoimmune diseases because of its (i) innate and adaptive immune response (ii) tissue homing properties (iii) production of IL-17A. These cells are predominantly CD8 cells, because of its strong association with MHC-I. Tc17 CD8+/MAIT cells likely to have a critical role in psoriatic arthritis (PsA).

IL-9 receptor: Regulatory role on FLS and pannus formation.

Objective: Functions of the Th9 cells and its signature cytokine IL-9 in human autoimmune diseases is currently under extensive research. Here we are reporting new functions of IL-9-receptor (IL-9R); its regulatory role on (i) FLS (fibroblast like synoviocyte) biology and (ii) pannus formation in rheumatoid arthritis (RA) and psoriatic arthritis (PsA).

Methods: RA, PsA, and OA synovial tissue biopsies were obtained; FLS were derived and cultured from these tissues.

Correction to: Inflammation, Atherosclerosis, and Psoriasis.

Following publication of this article [1] it came to our attention that we neglected to reference an article by Ishwarlal Jialal published in Critical Pathways in Cardiology [2].

Janus kinase/signal transducer and activator of transcription pathways in spondyloarthritis.

Purpose Of Review: Cytokines are major drivers of autoimmunity, and biologic agents targeting cytokines have revolutionized the treatment of immune-mediated diseases. Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway represents a group of several intracellular molecules with a key role in signal pathways activated by growth factors and cytokines. These kinase proteins are associated with the signaling process of multiple key cytokines, which regulates various T-cell subpopulations and their effector cytokines.

Mechanistic rationales for targeting interleukin-17A in spondyloarthritis.

The term spondyloarthritis (SpA) is used to describe a group of inflammatory autoimmune diseases, including ankylosing spondylitis and psoriatic arthritis, with common genetic risk factors and clinical features. SpA is clinically distinct from rheumatoid arthritis and typically affects the spine, sacroiliac joints, entheses, and, less commonly, peripheral joints. Although the pathogenesis of SpA is not fully understood, recent findings have identified the interleukin (IL)-17 pathway as a key mediator of disease pathogenesis.

Management of psoriatic arthritis: Early diagnosis, monitoring of disease severity and cutting edge therapies.

Psoriatic arthritis (PsA) is a heterogeneous disease that can involve a variety of distinct anatomical sites including a patient's peripheral and axial joints, entheses, skin and nails. Appropriate management of PsA requires early diagnosis, monitoring of disease activity, and utilization of cutting edge therapies. To accomplish the former there are a variety of PsA-specific tools available to screen, diagnose, and assess patients.

IL-23/IL-17 axis in spondyloarthritis-bench to bedside.

Cytokines play a critical role in the pathogenesis of psoriatic arthritis, ankylosing spondylitis, and other types of spondyloarthritis (SpA). Besides IFN-γ and TNF-α; IL-23/IL-17 cytokines play a dominant role in the inflammatory and proliferative cascades of SpA. Recently, in a series of elegant experiments using mouse models and human tissues, it has been demonstrated that IL-23-induced Th17 cytokines (IL-17 and IL-22) can contribute to following pathologic events associated with SpA: development of psoriatic plaque, pannus formation in the joint, joint erosion, and new bone formation.