Project description:Purpose of reviewThis review presents an overview of the current knowledge of TRAF molecules in inflammation with an emphasis on available human evidence and direct in vivo evidence of mouse models that demonstrate the contribution of TRAF molecules in the pathogenesis of inflammatory diseases.Recent findingsThe tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family of cytoplasmic proteins was initially identified as signaling adaptors that bind directly to the intracellular domains of receptors of the TNF-R superfamily. It is now appreciated that TRAF molecules are widely employed in signaling by a variety of adaptive and innate immune receptors as well as cytokine receptors. TRAF-dependent signaling pathways typically lead to the activation of nuclear factor-κBs (NF-κBs), mitogen-activated protein kinases (MAPKs), or interferon-regulatory factors (IRFs). Most of these signaling pathways have been linked to inflammation, and therefore TRAF molecules were expected to regulate inflammation and inflammatory responses since their discovery in 1990s. However, direct in vivo evidence of TRAFs in inflammation and especially in inflammatory diseases had been lacking for many years, partly due to the difficulty imposed by early lethality of TRAF2-/-, TRAF3-/-, and TRAF6-/- mice. With the creation of conditional knockout and lineage-specific transgenic mice of different TRAF molecules, our understanding about TRAFs in inflammation and inflammatory responses has rapidly advanced during the past decade.SummaryIncreasing evidence indicates that TRAF molecules are versatile and indispensable regulators of inflammation and inflammatory responses and that aberrant expression or function of TRAFs contributes to the pathogenesis of inflammatory diseases.

| S-EPMC5839642 | biostudies-literature

Disrupted regulatory T cell homeostasis in inflammatory bowel diseases.

Project description:In the gut, where billions of non-self-antigens from the food and the microbiota are present, the immune response must be tightly regulated to ensure both host protection against pathogenic microorganisms and the absence of immune-related pathologies. It has been well documented that regulatory T cells (Tregs) play a pivotal role in this context. Indeed, Tregs are able to prevent excessive inflammation, which can lead to the rupture of intestinal homeostasis observed in inflammatory bowel diseases (IBDs). Both the worldwide incidence and prevalence of such diseases have increased throughout the latter part of the 20(th) century. Therefore, it is crucial to understand how Tregs suppress the colitogenic immune cells to establish new treatments for patients suffering from IBDs. In this review, we will first summarize the results obtained in animal model studies that highlight the importance of Tregs in maintaining intestinal homeostasis and describe the specific suppressive mechanisms involved. Next, our current knowledge about Tregs contribution to human IBDs will be reviewed, as well as the current therapeutic perspective on using Tregs for clinical IBD treatment and the challenges that remain to be resolved to ensure both the safety and effectiveness of these therapies in targeting this critical immune-regulatory cell population.

| S-EPMC4716049 | biostudies-literature

Editorial: Epigenetic Regulation in Cardiovascular Diseases.

Project description: Not available

| S-EPMC8787130 | biostudies-literature

Editorial: Casein kinases in human diseases.

Project description: Not available

| S-EPMC9755584 | biostudies-literature

Editorial: Molecular mechanisms of neuropsychiatric diseases.

Project description: Not available

| S-EPMC9773978 | biostudies-literature

Editorial: Autoimmune blistering diseases, volume II.

Project description: Not available

| S-EPMC10061345 | biostudies-literature

Inflammation, Autoinflammation and Autoimmunity in Inflammatory Bowel Diseases.

Project description:In this review, the role of innate and adaptive immunity in the pathogenesis of inflammatory bowel diseases (IBD) is reported. In IBD, an altered innate immunity is often found, with increased Th17 and decreased Treg cells infiltrating the intestinal mucosa. An associated increase in inflammatory cytokines, such as IL-1 and TNF-α, and a decrease in anti-inflammatory cytokines, such as IL-10, concur in favoring the persistent inflammation of the gut mucosa. Autoinflammation is highlighted with insights in the role of inflammasomes, which activation by exogenous or endogenous triggers might be favored by mutations of NOD and NLRP proteins. Autoimmunity mechanisms also take place in IBD pathogenesis and in this context of a persistent immune stimulation by bacterial antigens and antigens derived from intestinal cells degradation, the adaptive immune response takes place and results in antibodies and autoantibodies production, a frequent finding in these diseases. Inflammation, autoinflammation and autoimmunity concur in altering the mucus layer and enhancing intestinal permeability, which sustains the vicious cycle of further mucosal inflammation.

| S-EPMC10378236 | biostudies-literature

Editorial: Recent Advances in Potential Biomarkers for Rheumatic Diseases and in Cell-Based Therapies in the Management of Inflammatory Rheumatic Diseases.

Project description: Not available

| S-EPMC8789740 | biostudies-literature