Search results for "Th1"

IL-17 and related cytokines involved in the pathology and immunotherapy of multiple sclerosis: Current and future developments.

2014

Multiple sclerosis (MS), an autoimmune neurological disorder, is driven by self-reactive T helper (Th) cells. Research on the role of Th17 lymphocytes in MS pathogenesis has made significant progress in identifying various immunological as well as environmental factors that induce the differentiation and expansion of these cells, different subsets of Th17 cells with varying degrees of pathogenicity, and the role of the secreted effector cytokines. While approved therapies for MS offer significant benefit to patients, there remain unmet needs. Ongoing clinical trials aim to translate the advanced knowledge of Th17 cytokines to improved therapies. This review discusses the current status and …

Self-adjuvanting C18 lipid vinil sulfone-PP2A vaccine: study of the induced immunomodulation against

2017

Despite the importance of the adjuvant in the immunization process, very few adjuvants merge with the antigens in vaccines. A synthetic self-adjuvant oleic-vinyl sulfone (OVS) linked to the catalytic region of recombinant serine/threonine phosphatase 2A from the nematode Angiostrongylus costaricensis (rPP2A) was used for intranasal immunization in mice previously infected with Trichuris muris. The animal intranasal immunization with rPP2A-OVS showed a reduction of 99.01% in the number of the nematode eggs and 97.90% in adult. The immunohistochemical analysis of the intestinal sections showed that in immunized animals with lipopeptide the mucus was significantly higher than in the other expe…

IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology.

2014

Gut homeostasis and mucosal immune defense rely on the differential contributions of dendritic cells (DC) and macrophages. Here we show that colonic CX3CR1+ mononuclear phagocytes are critical inducers of the innate response to Citrobacter rodentium infection. Specifically, the absence of IL-23 expression in macrophages or CD11b+ DC results in the impairment of IL-22 production and in acute lethality. Highlighting immunopathology as a death cause, infected animals are rescued by the neutralization of IL-12 or IFNγ. Moreover, mice are also protected when the CD103+ CD11b− DC compartment is rendered deficient for IL-12 production. We show that IL-12 production by colonic CD103+ CD11b− DC is r…

The action of TH17 cells on blood brain barrier in multiple sclerosis and experimental autoimmune encephalomyelitis.

2019

Th17 cells, known as a highly pro-inflammatory subtype of Th cells, are involved very early in numerous aspects of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) neuropathology. A crucial event for the formation and accumulation of MS lesions is represented by the disruption of the blood brain barrier (BBB) in relapsing-remitting MS. Th17 cells also contribute to the progression of MS/EAE. These events will allow for the passage of inflammatory cells into the brain. Secondary to this, increased recruitment of neutrophils occurs, followed by increased protease activity that will continue to attract macrophages and monocytes, leading to brain inflammation with sus…

Mucosal immunology and probiotics.

2013

The cross-talk between the mucosa-associated immune system and microbiota is critical in mucosal tissue homeostasis as well as in protection against infectious and inflammatory diseases occurring at mucosal sites. This recent evidence has paved the way to therapeutic approaches aimed at modulating the mucosa-associated immune system using probiotics. Different strains of probiotics possess the ability to finely regulate dendritic cell (DC) activation, polarizing the subsequent T cell activity toward Th1 (e.g. Lactobacillus (Lb) acidophilus), Th2 (Lb.reuteri and Bifidobacterium bifidum) or, as more recently demonstrated, Th17 responses induced by specific strains such as Lb.rhamnosus GG and …

Advances in leishmaniasis immunopathogenesis

2011

The phosphodiesterase 4 inhibitor roflumilast augments the Th17-promoting capability of dendritic cells by enhancing IL-23 production, and impairs th…

2016

Phosphodiesterase 4 (PDE4) inhibitors serve to prevent degradation of the intracellular second messenger cAMP, resulting in broad anti-inflammatory effects on different cell types including immune cells. Agents that elevate cAMP levels via activation of adenylate cyclase have been shown to imprint a Th17-promoting capacity in dendritic cells (DCs). Therefore, we studied the potential of therapeutically relevant PDE inhibitors to induce a pronounced Th17-skewing capacity in DCs. Here we show that mouse bone marrow-derived (BM-) DCs when treated with the PDE4 inhibitor roflumilast (ROF, trade name: Daxas) in the course of stimulation with LPS (ROF-DCs) evoked elevated IL-17 levels in cocultur…

Dense Bodies of Human Cytomegalovirus Induce both Humoral and Cellular Immune Responses in the Absence of Viral Gene Expression

2000

ABSTRACTInfection of fibroblast cell cultures with human cytomegalovirus (HCMV) leads to the production of significant amounts of defective enveloped particles, termed dense bodies (DB). These noninfectious structures contain major antigenic determinants which are responsible for induction of both the humoral and the cellular immune response against HCMV. We tested the hypothesis that, by virtue of their unique antigenic and structural properties, DB could induce a significant immune response in the absence of infectious virus. Mice were immunized with gradient-purified DB, which were either left untreated or subjected to sequential rounds of sonication and freeze-thawing to prevent cellula…

Dermal dendritic cells, but not Langerhans cells, are critical in murine single epicutaneous sensitization

2014

A murine repeated protein-patch model has been established to study epicutaneous sensitization in atopic dermatitis. This model has shown a predominant Th2 and a weak Th1 response in both BALB/c and C57BL/6 mice. However, Th responses induced in the repeated model are not consistent with the generally accepted theory that BALB/c and C57BL/6 mice are Th2 and Th1 prone and are representatives of human atopy and non-atopy, respectively. In this study, a single protein-patch model was established, which showed in addition to the Th2 response, a remarkable Th1 response in C57BL/6 mice, but not in BALB/c mice. Moreover, using muLangerin-DTR mice, we demonstrated that dermal dendritic cells, but n…

Mouse models for multiple sclerosis: historical facts and future implications.

2011

AbstractMultiple sclerosis (MS) is an inflammatory and demyelinating condition of the CNS, characterized by perivascular infiltrates composed largely of T lymphocytes and macrophages. Although the precise cause remains unknown, numerous avenues of research support the hypothesis that autoimmune mechanisms play a major role in the development of the disease. Pathologically similar lesions to those seen in MS can be induced in laboratory rodents by immunization with CNS-derived antigens. This form of disease induction, broadly termed experimental autoimmune encephalomyelitis, is frequently the starting point in MS research with respect to studying pathogenesis and creating novel treatments. M…