Clec12a controls colitis by tempering inflammation and restricting expansion of specific commensals.

Microbiota composition regulates colitis severity, yet the innate immune mechanisms that control commensal communities and prevent disease remain unclear. We show that the innate immune receptor, Clec12a, impacts colitis severity by regulating microbiota composition. Transplantation of microbiota from a Clec12a animal is sufficient to worsen colitis in wild-type mice.

Clec12a tempers inflammation while restricting expansion of a colitogenic commensal.

Regulation of the microbiota is critical to intestinal health yet the mechanisms employed by innate immunity remain unclear. Here we show that mice deficient in the C-Type-lectin receptor, Clec12a developed severe colitis, which was dependent on the microbiota. Fecal-microbiota-transplantation (FMT) studies into germfree mice revealed a colitogenic microbiota formed within Clec12a mice that was marked by expansion of the gram-positive organism, .

A Stk4-Foxp3-NF-κB p65 transcriptional complex promotes T cell activation and homeostasis.

The molecular programs involved in regulatory T (T) cell activation and homeostasis remain incompletely understood. Here, we show that T cell receptor (TCR) signaling in T cells induces the nuclear translocation of serine/threonine kinase 4 (Stk4), leading to the formation of an Stk4-NF-κB p65-Foxp3 complex that regulates Foxp3- and p65-dependent transcriptional programs. This complex was stabilized by Stk4-dependent phosphorylation of Foxp3 on serine-418.

Differential Multi-cellularity Is Required for the Adaptation for to Withstand Heavy Metals Toxicity.

is a multi-metal tolerant bacteria, isolated from the paddy rhizospheric soil sample. Upon the multiple metal toxicity, altered their phenotypic/morphogenesis. Here we examined the effects of cadmium (Cd2+), chromium (Cr2+), and mercury (Hg2+) on the morphogenesis of in comparison to control.

Notch4 signaling limits regulatory T-cell-mediated tissue repair and promotes severe lung inflammation in viral infections.

A cardinal feature of COVID-19 is lung inflammation and respiratory failure. In a prospective multi-country cohort of COVID-19 patients, we found that increased Notch4 expression on circulating regulatory T (Treg) cells was associated with disease severity, predicted mortality, and declined upon recovery. Deletion of Notch4 in Treg cells or therapy with anti-Notch4 antibodies in conventional and humanized mice normalized the dysregulated innate immunity and rescued disease morbidity and mortality induced by a synthetic analog of viral RNA or by influenza H1N1 virus.

Author Correction: A regulatory T cell Notch4-GDF15 axis licenses tissue inflammation in asthma.

A Correction to this paper has been published: https://doi.org/10.1038/s41590-021-00929-x.

The microbial origins of food allergy.

Food allergy (FA) is a significant public health issue, propelled by its rapidly increasing prevalence. Its sharp rise into prominence has focused attention on causative environmental factors and their interplay with the immune system in disease pathogenesis. In that regard, there is now substantial evidence that alterations in the gut microbiome early in life imprint the host gut mucosal immunity and may play a critical role in precipitating FA.

Regulatory T Cell-Derived TGF-β1 Controls Multiple Checkpoints Governing Allergy and Autoimmunity.

The mechanisms by which regulatory T (Treg) cells differentially control allergic and autoimmune responses remain unclear. We show that Treg cells in food allergy (FA) had decreased expression of transforming growth factor beta 1 (TGF-β1) because of interleukin-4 (IL-4)- and signal transducer and activator of transciription-6 (STAT6)-dependent inhibition of Tgfb1 transcription. These changes were modeled by Treg cell-specific Tgfb1 monoallelic inactivation, which induced allergic dysregulation by impairing microbiota-dependent retinoic acid receptor-related orphan receptor gamma t (ROR-γt) Treg cell differentiation.

A regulatory T cell Notch4-GDF15 axis licenses tissue inflammation in asthma.

Elucidating the mechanisms that sustain asthmatic inflammation is critical for precision therapies. We found that interleukin-6- and STAT3 transcription factor-dependent upregulation of Notch4 receptor on lung tissue regulatory T (T) cells is necessary for allergens and particulate matter pollutants to promote airway inflammation. Notch4 subverted T cells into the type 2 and type 17 helper (T2 and T17) effector T cells by Wnt and Hippo pathway-dependent mechanisms.

Regulatory T cells do not suppress rather activate human basophils by IL-3 and STAT5-dependent mechanisms.

Basophils play an important role in orienting Th2 immune response, and in the pathogenesis of allergic and inflammatory disorders. However, the mechanism by which basophils are kept in check remains unclear and hence we explored the role of regulatory T cells (Treg cells) in this process. We demonstrate that human Treg cells do not suppress rather induce activation of basophils, and promote Th2 responses by IL-3 and STAT5-dependent mechanism.

The Role of RodA-Conserved Cysteine Residues in the Conidial Surface Organization.

Immune inertness of conidia is attributed to its surface rodlet-layer made up of RodAp, characterized by eight conserved cysteine residues forming four disulfide bonds. Earlier, we showed that the conserved cysteine residue point (ccrp mutations result in conidia devoid of the rodlet layer. Here, we extended our study comparing the surface organization and immunoreactivity of conidia carrying ccrp-mutations with the deletion mutant (∆).

Dietary and Microbial Determinants in Food Allergy.

The steep rise in food allergy (FA) has evoked environmental factors involved in disease pathogenesis, including the gut microbiota, diet, and their metabolites. Early introduction of solid foods synchronizes with the "weaning reaction," a time during which the microbiota imprints durable oral tolerance. Recent work has shown that children with FA manifest an early onset dysbiosis with the loss of Clostridiales species, which promotes the differentiation of ROR-γt regulatory T cells to suppress FA.

Potential of regulatory T-cell-based therapies in the management of severe COVID-19.

https://bit.ly/3eKqWPo

Intravenous immunoglobulin mediates anti-inflammatory effects in peripheral blood mononuclear cells by inducing autophagy.

Autophagy plays an important role in the regulation of autoimmune and autoinflammatory responses of the immune cells. Defective autophagy process is associated with various autoimmune and inflammatory diseases. Moreover, in many of these diseases, the therapeutic use of normal immunoglobulin G or intravenous immunoglobulin (IVIG), a pooled normal IgG preparation, is well documented.

Correction: Saha, C., et al. Differential Effects of Preparations on the Maturation and Activation of Human Dendritic Cells and CD4 T Cell Responses. 2016, , 912.

The authors wish to make the following corrections to this paper [...

Author Correction: Microbiota therapy acts via a regulatory T cell MyD88/RORγt pathway to suppress food allergy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Functional reprogramming of regulatory T cells in the absence of Foxp3.

Regulatory T cells (T cells) deficient in the transcription factor Foxp3 lack suppressor function and manifest an effector T (T) cell-like phenotype. We demonstrate that Foxp3 deficiency dysregulates metabolic checkpoint kinase mammalian target of rapamycin (mTOR) complex 2 (mTORC2) signaling and gives rise to augmented aerobic glycolysis and oxidative phosphorylation. Specific deletion of the mTORC2 adaptor gene Rictor in Foxp3-deficient T cells ameliorated disease in a Foxo1 transcription factor-dependent manner.

Regulation of oral immune tolerance by the microbiome in food allergy.

The steep rise in the incidence and prevalence of food allergy (FA) in the last few decades have focused attention of environmental mechanisms which act to promote disease, chief among which is the microbiome. Recent studies have now established the presence of pathogenic dysbiosis in FA that could be precipitated by a variety of environmental insults, including among others antibiotic usage and mode of delivery, that act to subvert the immune regulatory response that enforce tolerance to dietary antigens. A key attribute of this dysbiosis is the loss of Clostridial bacterial species that act to promote the formation of food allergen-specific nascent regulatory T cells in the gut.

Microbiota therapy acts via a regulatory T cell MyD88/RORγt pathway to suppress food allergy.

The role of dysbiosis in food allergy (FA) remains unclear. We found that dysbiotic fecal microbiota in FA infants evolved compositionally over time and failed to protect against FA in mice. Infants and mice with FA had decreased IgA and increased IgE binding to fecal bacteria, indicative of a broader breakdown of oral tolerance than hitherto appreciated.

Assembly and disassembly of conidial rodlets.

The rodlet structure present on the conidial surface hides conidia from immune recognition. In spite of the essential biological role of the rodlets, the molecular basis for their self-assembly and disaggregation is not known. Analysis of the soluble forms of conidia-extracted and recombinant RodA by NMR spectroscopy has indicated the importance of disulfide bonds and identified two dynamic regions as likely candidates for conformational change and intermolecular interactions during conversion of RodA into the amyloid rodlet structure.