Search results for "Immunity"

2016

AbstractStem cells control their mitotic activity to decide whether to proliferate or to stay in quiescence. Drosophila neural stem cells (NSCs) are quiescent at early larval stages, when they are reactivated in response to metabolic changes. Here we report that cell-contact inhibition of growth through the canonical Hippo signalling pathway maintains NSC quiescence. Loss of the core kinases hippo or warts leads to premature nuclear localization of the transcriptional co-activator Yorkie and initiation of growth and proliferation in NSCs. Yorkie is necessary and sufficient for NSC reactivation, growth and proliferation. The Hippo pathway activity is modulated via inter-cellular transmembran…

Context- and Tissue-Specific Regulation of Immunity and Tolerance by Regulatory T Cells

2016

The immune system has evolved to defend the organism against an almost infinite number of pathogens in a locally confined and antigen-specific manner while at the same time preserving tolerance to harmless antigens and self. Regulatory T (Treg) cells essentially contribute to an immunoregulatory network preventing excessive immune responses and immunopathology. There is emerging evidence that Treg cells not only operate in secondary lymphoid tissue but also regulate immune responses directly at the site of inflammation. Hence, the classification of Treg cells might need to be further extended by Treg cell subsets that are functionally and phenotypically polarized by their residency. In this…

Cnidarian Immunity and the Repertoire of Defense Mechanisms in Anthozoans

2020

Anthozoa is the most specious class of the phylum Cnidaria that is phylogenetically basal within the Metazoa. It is an interesting group for studying the evolution of mutualisms and immunity, for despite their morphological simplicity, Anthozoans are unexpectedly immunologically complex, with large genomes and gene families similar to those of the Bilateria. Evidence indicates that the Anthozoan innate immune system is not only involved in the disruption of harmful microorganisms, but is also crucial in structuring tissue-associated microbial communities that are essential components of the cnidarian holobiont and useful to the animal’s health for several functions including metabolism, imm…

Invariant NKT Cells and Rheumatic Disease: Focus on Primary Sjogren Syndrome.

2019

Primary Sjogren syndrome (pSS) is a complex autoimmune disease mainly affecting salivary and lacrimal glands. Several factors contribute to pSS pathogenesis; in particular, innate immunity seems to play a key role in disease etiology. Invariant natural killer (NK) T cells (iNKT) are a T-cell subset able to recognize glycolipid antigens. Their function remains unclear, but studies have pointed out their ability to modulate the immune system through the promotion of specific cytokine milieu. In this review, we discussed the possible role of iNKT in pSS development, as well as their implications as future markers of disease activity.

Enterococcus hirae and Barnesiella intestinihominis Facilitate Cyclophosphamide-Induced Therapeutic Immunomodulatory Effects.

2016

International audience; The efficacy of the anti-cancer immunomodulatory agent cyclophosphamide (CTX) relies on intestinal bacteria. How and which relevant bacterial species are involved in tumor immunosurveillance, and their mechanism of action are unclear. Here, we identified two bacterial species, Enterococcus hirae and Barnesiella intestinihominis that are involved during CTX therapy. Whereas E. hirae translocated from the small intestine to secondary lymphoid organs and increased the intratumoral CD8/ Treg ratio, B. intestinihominis accumulated in the colon and promoted the infiltration of IFN-gamma-producing gamma delta Tau cells in cancer lesions. The immune sensor, NOD2, limited CTX…

Nutritional control of IL-23/Th17-mediated autoimmune disease through HO-1/STAT3 activation

2017

AbstractThe nutritional curcumin (CUR) is beneficial in cell-mediated autoimmune diseases. The molecular mechanisms underlying this food-mediated silencing of inflammatory immune responses are poorly understood. By investigating antigen-specific immune responses we found that dietary CUR impairs the differentiation of Th1/Th17 cells in vivo during encephalomyelitis and instead promoted Th2 cells. In contrast, feeding CUR had no inhibitory effect on ovalbumin-induced airway inflammation. Mechanistically, we found that CUR induces an anti-inflammatory phenotype in dendritic cells (DC) with enhanced STAT3 phosphorylation and suppressed expression of Il12b and Il23a. On the molecular level CUR …

TET3 prevents terminal differentiation of adult NSCs by a non-catalytic action at Snrpn.

2019

Ten-eleven-translocation (TET) proteins catalyze DNA hydroxylation, playing an important role in demethylation of DNA in mammals. Remarkably, although hydroxymethylation levels are high in the mouse brain, the potential role of TET proteins in adult neurogenesis is unknown. We show here that a non-catalytic action of TET3 is essentially required for the maintenance of the neural stem cell (NSC) pool in the adult subventricular zone (SVZ) niche by preventing premature differentiation of NSCs into non-neurogenic astrocytes. This occurs through direct binding of TET3 to the paternal transcribed allele of the imprinted gene Small nuclear ribonucleoprotein-associated polypeptide N (Snrpn), contr…

SPARC regulation of PMN clearance protects from pristane-induced lupus and rheumatoid arthritis

2021

Summary The secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein with unexpected immunosuppressive function in myeloid cells. We investigated the role of SPARC in autoimmunity using the pristane-induced model of lupus that, in mice, mimics human systemic lupus erythematosus (SLE). Sparc−/− mice developed earlier and more severe renal disease, multi-organ parenchymal damage, and arthritis than the wild-type counterpart. Sparc+/- heterozygous mice showed an intermediate phenotype suggesting Sparc gene dosage in autoimmune-related events. Mechanistically, reduced Sparc expression in neutrophils blocks their clearance by macrophages, through defective delivery of don'…

Differential proteomics reveals age-dependent liver oxidative costs of innate immune activation in mice

2016

Abstract Individual response to an immune challenge results from the optimization of a trade-off between benefits and costs of immune cell activation. Age-related immune disorders may have several mechanistic bases, from immune cell defects to chronic pro-inflammatory status and oxidative imbalance, but we are still lacking experimental data showing the relative importance of each of these mechanisms. Using a proteomic approach and subsequent biochemical validations of proteomics-derived hypotheses, we found age-dependent regulations in the liver of 3-months and 1-year old-mice in response to an acute innate immune activation. Old mice presented a chronic up-regulation of several proteins i…

Innate and Adaptive Immunity in Aging and Longevity: The Foundation of Resilience

2020

The interrelation of the processes of immunity and senescence now receives an unprecedented emphasis during the COVID-19 pandemic, which brings to the fore the critical need to combat immunosenescence and improve the immune function and resilience of older persons. Here we review the historical origins and the current state of the science of innate and adaptive immunity in aging and longevity. From the modern point of view, innate and adaptive immunity are not only affected by aging but also are important parts of its underlying mechanisms. Excessive levels or activity of antimicrobial peptides, C-reactive protein, complement system, TLR/NF-κB, cGAS/STING/IFN 1,3 and AGEs/RAGE pathways, mye…