Abstract Emerging evidence has demonstrated that CD4+ T cells infiltrate into the substantia nigra (SN) in Parkinson's disease (PD) patients and animal models of PD. SN-infiltrated bearing inflammatory phenotypes promote microglial activation strongly contribute to neurodegeneration dopaminergic neurons. Importantly, altered expression dopamine receptor D3 (D3R) PBLs from PD been correlated with severity. Moreover, pharmacological suggested D3R is involved IFN-γ production by human cells. In...

Abstract Dendritic cells (DCs) are responsible for priming T and promoting their differentiation from naive into appropriate effector cells. Emerging evidence suggests that neurotransmitters can modulate cell-mediated immunity. However, the involvement of specific or receptors remains poorly understood. In this study, we analyzed role dopamine in regulation DC function. We found DCs express as well machinery necessary to synthesize, store, degrade dopamine. Notably, expression D5R decreased...

Respiratory syncytial virus (RSV) infection is one of the leading causes infant hospitalization and a major health economic burden worldwide. Infection with this induces an exacerbated innate proinflammatory immune response characterized by abundant cell infiltration into airways lung tissue damage. RSV also impairs induction adequate adaptive T response, which favors pathogenesis. Unfortunately, to date there are no efficient vaccines against virus. Recent in vitro vivo studies suggest that...

As it has been established that demethylation of lysine 27 histone H3 by the lysine-specific demethylase JMJD3 increases immune responses and thus elicits inflammation, we hypothesize inhibition may attenuate autoimmune disorders. We found in vivo administration GSK-J4, a selective inhibitor UTX, ameliorates severity experimental encephalomyelitis (EAE). In vitro experiments revealed anti-inflammatory effect GSK-J4 was exerted through an on dendritic cells (DCs), promoting tolerogenic...

Abstract Dopamine receptor D3 (DRD3) expressed on CD4+ T cells is required to promote neuroinflammation in a murine model of Parkinson’s disease. However, how DRD3 signaling affects cell–mediated immunity remains unknown. In this study, we report that TCR stimulation mouse induces expression, regardless the lineage specification. Importantly, functional analyses performed vivo using adoptive transfer OVA-specific OT-II into wild-type recipients show deficiency results attenuated...

Neuroinflammation constitutes a fundamental process involved in Parkinson's disease (PD). Microglial cells play central role the outcome of neuroinflammation and consequent neurodegeneration dopaminergic neurons substantia nigra. Current evidence indicates that CD4+ T-cells infiltrate brain PD, where they critical determining functional phenotype microglia, thus regulating progression disease. We previously demonstrated mice bearing dopamine receptor D3 (DRD3)-deficient are completely...

Background/Objectives: In Latin America, yerba mate (YM) is a popular infusion processed from the leaves and stems of Ilex paraguariensis. YM has been shown to have anti-inflammatory properties in several studies, although effect on multiple sclerosis (MS) remains elusive. The purpose this study was examine development MS, by using experimental autoimmune encephalomyelitis (EAE) mouse model while also evaluating its over infiltration immune cells into central nervous system (CNS) regulatory...

Increasing evidence shows that antigen-presenting cells (APCs) are involved in the development of inflammation associated to hypertension. However, potential role APCs modulation renal sodium transport has not been addressed. We hypothesized participate and, thus, high blood pressure response angiotensin II plus a high-salt diet. Using transgenic mice allow ablation CD11c APCs, we studied transport, intrarenal renin–angiotensin system components, pressure, and cardiac/renal tissue damage...

The dual potential to promote tolerance or inflammation self-antigens makes dendritic cells (DCs) fundamental players in autoimmunity. Previous results have shown that stimulation of dopamine receptor D5 (DRD5) DCs potentiates their inflammatory behaviour, favouring the development experimental autoimmune encephalomyelitis (EAE). Here we aimed decipher underlying mechanism and test its relevance multiple sclerosis (MS) patients. Our data shows DRD5-deficiency confined EAE mice resulted...

A number of studies have shown pharmacologic evidence indicating that stimulation type I dopamine receptor (DR), favors T-helper-17 (Th17)-mediated immunity involved in experimental autoimmune encephalomyelitis (EAE) and some other inflammatory disorders. Nevertheless, the lack drugs might discriminate between DRD1 DRD5 has made pharmacological distinction two receptors difficult. We previously genetic demonstrating a relevant role DRD5-signaling dendritic cells (DCs) favoring CD4+...

Adaptive immunity is crucial in cardiovascular and renal inflammation/fibrosis upon hyperactivation of mineralocorticoid receptor. We have previously demonstrated that dendritic cells can respond to receptor activation, the neutrophil gelatinase-associated lipocalin (NGAL) highly increased during aldosterone (Aldo)/mineralocorticoid receptor-dependent damage. However, interrelationship among cells, target organs induced by receptor, NGAL-dependence remains unknown.We studied role tissue...

Dendritic cells (DCs) promote T-cell mediated tolerance to self-antigens and induce inflammation innocuous-antigens. This dual potential makes DCs fundamental players in inflammatory disorders. Evidence from colitis mouse models bowel diseases (IBD) patients indicated that gut IBD is driven mainly by T-helper-1 (Th1) Th17 cells, suggesting an essential role for the development of IBD. Here we show GSK-J4, a selective inhibitor histone demethylase JMJD3/UTX, attenuated reducing increasing...

Abstract Introduction Gut microbiota plays a critical role in the regulation of immune homeostasis. Accordingly, several autoimmune disorders have been associated with dysbiosis gut microbiota. Notably, central nervous system (CNS) autoimmunity involves substantial reduction bacteria belonging to Clostridia clusters IV and XIVa, which constitute major producers short-chain fatty acids (SCFAs). Here we addressed surface receptor-mediated effects SCFAs on mucosal T-cells development CNS...

Background and AimsCD4+ T cells constitute central players in inflammatory bowel diseases (IBDs), driving inflammation the gut mucosa. Current evidence indicates that CCR9 integrin α4β7 are necessary sufficient to imprint colonic homing on CD4+ upon inflammation. Interestingly, dopaminergic signaling has been previously involved leukocyte homing. Despite dopamine levels strongly reduced inflamed mucosa, role of remains unknown. Here, we study how affects inflammation.MethodsGut was induced...

Summary Human respiratory syncytial virus ( hRSV ) is the leading cause of infant hospitalization related to disease. Infection with produces abundant infiltration immune cells into airways, which combined an exacerbated pro‐inflammatory response can lead significant damage lungs. RSV re‐infection extremely frequent, suggesting that this may have evolved molecular mechanisms interfere host adaptive immunity. be reduced by administering a humanized neutralizing antibody against fusion protein...

Inflammatory bowel diseases (IBD) are a group of chronic inflammatory conditions the gastrointestinal tract associated with multiple pathogenic factors, including dysregulation immune response. Effector CD4+ T cells and regulatory (Treg) central players in maintaining balance between tolerance inflammation. Interestingly, genetic modifications these have been implicated regulating commitment specific phenotypes functions. However, transcriptional program controlling behavior helper IBD...

Dendritic cells (DCs) have the ability to induce tolerance or inflammation in response self-antigens, which makes them fundamental players autoimmunity. In this regard, immunogenic DCs produce IL-12 and IL-23 favouring acquisition of Th1 Th17 inflammatory phenotypes, respectively, by autoreactive CD4+ T-cells, thus promoting Conversely, tolerogenic IL-10 TGF-β, inducing generation T-cells with suppressive activity (Treg), promote self-constituents. Previous studies shown that STAT3...