T helper (TH) 17 cells are believed to play a pivotal role in development of inflammatory bowel disease, and their contribution intestinal inflammation has been studied various models colitis. TH17 produce range cytokines, some which potential targets for immunotherapy. However, blockade IL-17A alone with secukinumab was not effective Crohn's disease. In this regard, the pathogenic impact versus IL-17F during is still unresolved.Development IFN-γ-producing, IL-17A-producing, IL-17F-producing...

Colitis is characterized by colonic inflammation and impaired gut health. Both features aggravate obesity insulin resistance. Host defense peptides (HDPs) are key regulators of homeostasis generally malfunctioning in above-mentioned conditions. We aimed here to improve bowel function diet-induced chemically induced colitis through daily oral administration lysozyme, a well-characterized HDP, derived from Acremonium alcalophilum.C57BL6/J mice were fed either low-fat reference diet or HFD ±...

Growing evidence supports the use of probiotics to prevent or mitigate obesity-related dysmetabolism and non-alcoholic fatty liver disease (NAFLD). However, frequent reports responders versus non-responders probiotic treatment warrant a better understanding key modifiers host–microbe interactions. The influence host diet on efficacy, in particular against metabolic diseases, remains elusive. We fed C57BL6/J mice low fat reference one two energy-matched high sucrose diets for 12 weeks;...

Abstract: Many different assays for measuring peptide–MHC interactions have been suggested over the years. Yet, there is no generally accepted standard method available. We recently generated preoxidized recombinant MHC class I molecules (MHC‐I) which can be purified to homogeneity under denaturing conditions (i.e., in absence of any contaminating peptides). Such denatured MHC‐I are functional equivalents “empty molecules”. When diluted into aqueous buffer containing beta‐2 microglobulin (β...

Using infections with lymphocytic choriomeningitis virus (LCMV) and vesicular stomatitis in mice as model systems, we have investigated the ability of antigen-primed CD8 + T cells generated context viral to produce IL-2. Our results indicate that acute immunizing infection normally leads generation high numbers IL-2-producing antigen-specific cells. By costaining for IL-2 IFN-γ intracellularly, found predominantly constitute a subset also producing IFN-γ. Comparison kinetics revealed appear...

BackgroundThe neurotransmitter substance P (SP) released by, and the transient receptor potential vanilloid (TRPV1), expressed by afferent nerves, have been implicated in mucosal neuro-immune-regulation. To test if enteric nerves are of importance for development chronic colitis, we examined antagonists high-affinity neurokinin 1 (NK-1) SP TRPV1 agonist capsaicin a T-cell transfer model colitis.

Probiotics may alter immune regulation. Recently, we showed that the probiotic bacteria Lactobacillus acidophilus NCFM™ influenced activity of regulatory T cells (Tregs) in vitro. The aim present work was to demonstrate if L. also affects function Tregs vivo.Development colitis after transfer CD4+CD25- and protection from by studied immunodeficient SCID mice which were simultaneously tube-fed with or salivarius Ls-33 for 5 weeks.Probiotic-fed transplanted low numbers addition...

Abstract Up to 25% of the US population harbor Clostridioides difficile in gut. Following antibiotic disruption gut microbiota, C. can act as an opportunistic pathogen and induce potentially lethal infections. Consequently, reducing colonization at-risk populations is warranted, prompting us identify characterize a probiotic candidate specifically targeting colonization. We identified Bacillus velezensis DSM 33864 promising strain reduce levels vitro. further investigated effects B. assay...

B cells positively contribute to immunity by antigen presentation CD4(+) T cells, cytokine production, and differentiation into antibody secreting plasma cells. Accumulating evidence implies that also possess immunoregulatory functions closely linked their capability of IL-10 secretion.Colitis development was followed in CD25(-) cell transplanted SCID mice co-transferred with exposed an enterobacterial extract (ebx-B cells). expression measured flow cytometry enzyme-linked immunosorbent...

Abstract Unfractionated CD4 + T cells from the gut‐associated lymphoid tissue (GALT) and peripheral lymph nodes are unresponsive when exposed to enterobacterial antigens in vitro . Under similar conditions, depleted vivo or of CD25 proliferate extensively. The – cell reactivity depends on MHC class II presentation, specific TCR stimulation, ligation, antigen processing by antigen‐presenting cells. respond autologousand heterologous antigens, but not feces germ‐free mice. Surprisingly,...

Scid mice transplanted with CD4+ T blast cells develop colitis. We investigated if the disease was influenced in colitic treated antibiotic and fed Lactobacillus spp. Colitic scid were for 1 week antibiotics (vancomycin/meropenem) followed or not by a 3-week administration of reuteri DSM-12246 rhamnosus 19070-2 at 2 × 109 live bacteria/mouse/24 hours. After 12 weeks, rectums removed histology, from mesenteric lymph nodes (MLN) polyclonally activated cytokine measurements. Irrespective no...

Summary Immunomodulatory dendritic cells (DCs) that induce antigen‐specific T‐cell tolerance upon in vivo adoptive transfer are promising candidates for immunotherapy of autoimmune diseases. The feasibility such a strategy has recently proved its efficacy animal models allotransplantation and experimental allergic encephalitis, but the effect inflammatory bowel disease not yet been demonstrated. In severe combined immunodeficient (SCID) mice, adoptively transferred CD4 + CD25 – T repopulate...

The ability of virus-specific CD8 + T cells to produce cytokines was studied in mice infected with lymphocytic choriomeningitis virus and vesicular stomatitis virus. Intracellular staining used visualize cytokine-producing CD4 cells. Overall, a similar range (IFN- γ , TNF- α IL-2, GM-CSF, RANTES, MIP-1 β ) as cells, but the relative distribution subsets is different. Moreover, were found dominate numerically at all time-points tested. Co-staining for more than one cytokine revealed that...

Summary Regulatory T (Treg) cells, derived from co‐cultures of unfractionated CD4 + cells and immature dendritic (DC), suppress enteroantigen‐induced proliferation CD25 − cells. The DC‐induced Treg are a mixture (10–20%) (80–90%) However, all the suppressor activity in vitro vivo resides T‐cell subset. can inhibit through transwell membrane, their function does not appear to depend on previous activation. display naïve phenotype, expressing high levels CD45RB l ‐selectin (CD62L). In...

The effect in vitro of six different probiotic strains including Lactobacillus acidophilus NCFM, salivarius Ls-33, paracasei subsp. YS8866441, plantarum Lp-115, Bifidobacterium bifidum BI-504 and BI-98 was studied on splenic enteroantigen-presenting cells (APC) CD4(+)CD25(+) T-regulatory (Tregs) splenocyte-T cell proliferation assays.Splenocytes exposed to enteroantigen +/- probiotics were used stimulate cultured CD4(+)CD25(-) T which titrated numbers Tregs added. Cytokine assays performed...

CD4+CD25− T cells induce severe colitis when injected into immunodeficient recipients. The migration of disease-inducing to the bowel is controlled by adhesion molecules and chemotactic proteins. Chemokine receptors expressed on are therefore potential targets for anti-inflammatory therapy in inflammatory disease. In this study, we have investigated role chemokine receptor CXCR3 development chronic a murine model. Expression CD4+ cell from normal colitic mice was assessed flow cytometry....

In the adoptive transfer model of colitis it has been shown that regulatory T cells (Treg) can hinder disease development and cure already existing mild colitis. The mechanisms underlying this effect CD4(+)CD25(+) Tregs are not well understood.To identify pathways importance for immune regulation in protected mice we studied genome-wide expression profile inflamed rectum SCID with CD4(+) cell uninflamed from by Treg cells. We used DNA microarray technology (Affymetrix GeneChip Mouse Genome...

Chemokines are small proteins involved in the direction of migration immune cells both during normal homeostasis and inflammation. have been implicated pathology many different inflammatory disorders therefore appealing therapeutic targets. Using a chemokine/chemokine receptor-specific gene expression profiling system 67 genes, authors determined profile chemokine receptor genes rectum colitic mice that protected fromcolitis by CD4CD25 regulatory T cells. In from colitis, found down...

Presentation of enterobacterial antigens by antigen-presenting cells and activation enteroantigen-specific CD4(+) T are considered crucial steps in inflammatory bowel disease (IBD) pathology. The detrimental effects such have been thoroughly demonstrated models colitis. Also, we previously established an vitro assay where murine colitogenic CD25(-) activated splenocytes pulsed with extract.CD4(+) were stimulated various kinds extract-pulsed cells. T-helper phenotypes detected flow...

Enteroantigens (eAgs) drive tolerogenic and inflammatory immune responses in the gut are of importance for sustained homeostasis colonic mucosa. Decline regulatory activity mucosa might result chronic colitis. B7-H4 is a co-inhibitory receptor expressed by professional antigen-presenting cells. By delivering signal 2 during T cell activation, it inhibits proliferation inflammation. In this study, we have used newly developed B7-H4-Ig fusion protein evaluated its effect on eAg-activated...

We have previously shown that conventional as well germ-free CD4+ T cells depleted of CD25+ from the gut-associated lymphoid tissue and periphery proliferate specifically in response to enterobacterial antigen exposure whereas unfractionated are not reactive under these conditions. Here we show majority enteroantigen-specific CD25- naive expressing a CD45RB high, CD62L high CD44 low phenotype. These also present thymus data adult thymectomized mice they represent late (>6 weeks) thymic...

Inflammatory bowel disease (IBD) is a multifactorial disorder with an unknown aetiology. The aim of this study to employ murine model IBD identify pathways and genes, which may play key role in the pathogenesis could be important for discovery new markers human disease. Here, we have investigated severe combined immunodeficient (SCID) mice, upon adoptive transfer concanavalin A-activated CD4(+) T cells develop inflammation colon predominance rectum. Mice increasing level was studied. RNA...