Neuropilin-1 surface expression discriminates between nT reg cells with stable expression and Nrp1 low iT reg cells showing inducible expression under inflammatory conditions.

Generation of anaphylaxis-inducing high affinity IgE requires sequential class switching.

Direct class switching to IgE generates IgE+ GC cells that are highly apoptotic and do not contribute to the memory compartment, while sequential switching through an IgG+ intermediate results in the generation of long-lived IgE+ plasma cells.

The headquarter of our immune system resides in the gut and modulates autoimmune disease activation in multiple sclerosis.

The gut microbiota modulates the autoimmune pathogenesis of type 1 diabetes (T1D) via mechanisms that remain largely unknown. The inflammasome components are innate immune sensors that are highly influenced by the gut environment and play pivotal roles in maintaining intestinal immune homeostasis. In this study we show that modifications of the gut microbiota induced by oral treatment with Lactobacillaceae-enriched probiotic VSL#3, alone or in combination with retinoic acid (RA), protect NOD mice from T1D by affecting inflammasome at the intestinal level. In particular, we show that VSL#3 treatment inhibits IL-1β expression while enhancing release of protolerogenic components of the inflammasome, such as indoleamine 2,3-dioxygenase (IDO) and IL-33. Those modifications of the intestinal microenvironment in VSL#3-treated NOD mice modulate gut immunity by promoting differentiation of tolerogenic CD103+ DCs and reducing differentiation/expansion of Th1 and Th17 cells in the intestinal mucosa and at the sites of autoimmunity, that is, within the pancreatic lymph nodes (PLN) of VSL#3-treated NOD mice. Our data provide a link between dietary factors, microbiota composition, intestinal inflammation, and immune homeostasis in autoimmune diabetes and could pave the way for new therapeutic approaches aimed at changing the intestinal microenvironment with probiotics to counterregulate autoimmunity and prevent T1D.

The production of IL-21 by T follicular helper (Tfh) cells is vital in driving the germinal centre reaction and high affinity antibody formation. However, the degree of Tfh cell heterogeneity and function is not fully understood. We used a novel IL-21eGFP reporter mouse strain to analyze the diversity and role of Tfh cells. Through the analysis of GFP expression in lymphoid organs of IL-21eGFP mice, we identified a subpopulation of GFP+, high IL-21 producing Tfh cells present only in Peyer’s Patches. GFP+Tfh cells were found to be polyclonal and related to GFP−Tfh cells of Peyer’s Patches in TCR repertoire composition and overall gene expression. Studies on the mechanisms of induction of GFP+Tfh cells demonstrated that they required the intestinal microbiota and a diverse repertoire of CD4+ T cells and B cells. Importantly, ablation of GFP+ cells resulted in a reduced frequency of Peyer’s Patches IgG1 and germinal center B cells in addition to small but significant shifts in gut microbiome composition. Our work highlights the diversity among IL-21 producing CD4+ Tfh cells, and the interrelationship between the intestinal bacteria and Tfh cell responses in the gut.

No abstract

ABSTRACT:Chemoprevention is a strategy to reduce the incidence of human cancer either by inhibiting initiation of carcinogenesis or by preventing exposure to carcinogens, by the use of plant or animal derived ingredients. In the present study we investigated the anticlastogenic effect of ethanol extract of Ulva fasciata, a green seaweed, against the chromosomal aberration and micronucleus induced by the anticancer drugs cyclophosphamide and mitomycin C. Three doses of extract (25, 50 and 75 mg/kg.b.w) was given by oral gavage for 5 days at 24 hr. intervals and on the 5 th day, CP (25 and 50mg/kg.b.w) or MMC (1 and 2mg/kg.b.w) were intraperitoneally injected and 24hrs. later micronucleus and chromosomal aberrations assays were performed. Our results show that Ulva extract gave significant protection against the CP and MMC induced damages by reducing micronucleus and chromosomal aberrations. The protection imparted by Ulva could be due to the synergistic and/or additive effects of biologically active ingredients present in the seaweed.