Search results for "Autoimmunity"
showing 10 items of 349 documents
TGF-β inhibitor Smad7 regulates dendritic cell-induced autoimmunity
2017
TGF-β is an anti-inflammatory cytokine whose signaling is negatively controlled by Smad7. Previously, we established a role for Smad7 in the generation of autoreactive T cells; however, the function of Smad7 in dendritic cells (DCs) remains elusive. Here, we demonstrate that DC-specific Smad7 deficiency resulted in elevated expression of the transcription factors Batf3 and IRF8, leading to increased frequencies of CD8(+)CD103(+) DCs in the spleen. Furthermore, Smad7-deficient DCs expressed higher levels of indoleamine 2,3-dioxygenase (IDO), an enzyme associated with tolerance induction. Mice devoid of Smad7 specifically in DCs are resistant to the development of experimental autoimmune ence…
AB0919 H-Ferritin and CD68+/H-ferritin+ Cells Are Increased in The Skin of Adult Onset Still's Disease Patients and Correlate with The Disease Activi…
2016
Background Adult onset Still9s disease (AOSD) is an inflammatory disease, characterized by high spiking fevers, arthritis, salmon-pink erythema and multivisceral involvement [1]. During AOSD, exceptionally high serum levels of ferritin may be observed and they might contribute to production of proinflammatory molecules [2]. Ferritin is composed by 24 subunits, heavy (H) subunits and light (L) subunits. The ferritin enriched in L subunits (L-ferritin) and the ferritin enriched in H subunits (H-ferritin) may be recognized in different tissues [3]. Objectives To investigate the skin tissue expression of both H-and L-ferritin and the number of macrophages expressing these molecules, in the infl…
Autoimmune aspects in glaucoma
2016
The pathogenesis of glaucoma, a common neurodegenerative disease, involves an immunologic component. Studies demonstrate changes of autoantibody concentrations against retinal and optic nerve head antigens in glaucoma patients. Furthermore we found antibody deposits in human glaucomatous retinae in a pro-inflammatory environment. Clinical studies showed up regulated, but also significantly down-regulated autoantibody levels. These antibodies belong to the natural autoimmunity. The upregulation of autoantibodies can be associated with fatal conditions, but several studies demonstrate that natural autoantibodies entail also neuroprotective characteristics and influence the protein expression …
EBI2 in splenic and local immune responses and in autoimmunity
2017
Abstract The seven transmembrane G protein-coupled receptor EBV-induced gene 2 (EBI2), also known as GPR183, is expressed in particular in immune cells. Activated by its endogenous ligands, which are a group of oxysterols, it functions as a chemo-attractant receptor, mediating cell migration. In coordination with other receptors, EBI2 plays important roles in controlling the migration of immune cells during the course of a T-dependent Ab response in the spleen. In recent years, it has become clear that EBI2 also has other roles to play in the immune system. Thus, EBI2 seems to be involved in innate immune responses, such as those mediated by TLR signaling, and it has been implicated in regi…
Rheostatic Functions of Mast Cells in the Control of Innate and Adaptive Immune Responses
2017
Mast cells are evolutionarily ancient cells, endowed with a unique developmental, phenotypic, and functional plasticity. They are resident cells that participate in tissue homeostasis by constantly sampling the microenvironment. As a result of their large repertoire of receptors, they can respond to multiple stimuli and selectively release different types and amounts of mediator. Here, we present and discuss the recent mast cell literature, focusing on studies that demonstrate that mast cells are more than a switch that is turned âoffâ when in the resting state and âonâ when in the degranulating state. We propose a new vision of mast cells in which, by operating in a ârheostaticâ…
Primary sjogren syndrome: Focus on innate immune cells and inflammation
2020
Primary Sjogren Syndrome (pSS) is a complex, multifactorial rheumatic disease that mainly targets salivary and lacrimal glands, inducing epithelitis. The cause behind the autoimmunity outbreak in pSS is still elusive; however, it seems related to an aberrant reaction to exogenous triggers such as viruses, combined with individual genetic pre-disposition. For a long time, autoantibodies were considered as the hallmarks of this disease; however, more recently the complex interplay between innate and adaptive immunity as well as the consequent inflammatory process have emerged as the main mechanisms of pSS pathogenesis. The present review will focus on innate cells and on the principal mechani…
Early inflammatory players in cutanous fibrosis.
2017
Systemic sclerosis (SSc) is one of the most complex systemic autoimmune diseases with multi-organ involvement and heterogeneous clinical manifestations. The exact etiology of SSc is still unknown. However, identified target structures are components of endothelial cells, the innate/adaptive immune systems and fibroblasts, resulting in the hallmarks of the disease in form of inflammation/autoimmunity, vasculopathy and fibrosis of the skin and internal organs. There has been a large body of evidence that the adaptive immune system with autoreactive T and B cells producing autoantibodies plays a central role in the pathogenesis of SSc but the role of earlier pathogenic processes involving the …
HSP60 is a ubiquitous player in the physiological and pathogenic interactions between the chaperoning and the immune systems
2017
HSP60 participates in many interactions between the system integrated by all chaperones and closely associated molecules (chaperoning system or CS) and the immune system (IS). These interactions occur constantly to maintain normal cell physiology but, occasionally, they are perturbed and become mediators of pathologic events that may lead to disease. This switch to pathology may be initiated by various factors, genetic or acquired, which cause qualitative and/or quantitative modifications of HSP60, or immune crossreactivity between the human and microbial chaperonin orthologs, or a break in the balance between the pro- and anti-inflammatory actions of the chaperonin. Thus, autoimmune and ch…
Targeted Activation of T Cells with IL-2-Coupled Nanoparticles
2020
Interleukin-2 (IL-2) is a T cell growth factor particularly required in regulatory T cell maintenance and memory T cell responses. High-dose IL-2 treatment was the first FDA-approved immunotherapy for cancer, while low-dose IL-2 administration has shown promise in allograft rejection and autoimmune and inflammatory diseases. However, its pleiotropic nature and the existence of IL-2 receptors with different binding affinity limit its therapeutic application. For an improved clinical applicability of the cytokine, a targeted receptor assignment must, therefore, be achieved. Nanoparticles allow controlling the location and dose of immunomodulating compounds and to specifically address specific…
Keratinocyte-derived IκBζ drives psoriasis and associated systemic inflammation.
2019
The transcriptional activator IκBζ is a key regulator of psoriasis, but which cells mediate its pathogenic effect remains unknown. Here we found that IκBζ expression in keratinocytes triggers not only skin lesions but also systemic inflammation in mouse psoriasis models. Specific depletion of IκBζ in keratinocytes was sufficient to suppress the induction of imiquimod- or IL-36–mediated psoriasis. Moreover, IκBζ ablation in keratinocytes prevented the onset of psoriatic lesions and systemic inflammation in keratinocyte-specific IL-17A–transgenic mice. Mechanistically, this psoriasis protection was mediated by IκBζ deficiency in keratinocytes abrogating the induction of specific proinflammato…