The anti-inflammatory and immune-modulatory effects of OEA limit DSS-induced colitis in mice

Fatty acid ethanolamides acting on proliferator-activated receptor (PPAR)-α are among the endogenous lipid molecules that attenuate inflammatory processes and pain sensitivity. Whereas these properties are well-known for palmitoylethanolamide (PEA), the efficacy of oleoylethanolamide (OEA, first described as a satiety hormone synthesized in the jejunum) has been overlooked. In this study, we aimed to evaluate the effect of OEA administration in a mouse model of colitis. C57BL/6J mice were exposed to 2.5% dextran sodium sulphate (DSS) in drinking water for 5 days. Daily i.p. administration of 10 mg/kg OEA started 3 days before DSS and lasted for 12 days. The DSS-untreated control group received only ultrapure water. DSS mice treated with OEA had a significant improvement of disease score. OEA restored mRNA transcription of PPAR-α, of tight junctions and protective factors of colon integrity disrupted by DSS. The improvement correlated with significant decrease of colonic and systemic levels of pro-inflammatory cytokines compared to the DSS group. OEA antiinflammatory effects were mediated by the selective targeting of the TLR4 axis causing a downstream inhibition of nuclear factor kappa B (NF-κB)- MyD88-dependent and NLRP3 inflammation pathways. OEA treatment also inhibited DSS-induced increase of inflammatory cytokines levels in the mesenteric lymph nodes. Conclusions and implications: These results underscore the validity of OEA as a potent protective and anti-inflammatory agent in ulcerative colitis that may be exploited to broaden the pharmacological strategies against inflammatory bowel disease

TCR repertoire diversity in Multiple Sclerosis: High-dimensional bioinformatics analysis of sequences from brain, cerebrospinal fluid and peripheral blood

BACKGROUND: T cells play a key role in the pathogenesis of multiple sclerosis (MS), a chronic, inflammatory, demyelinating disease of the central nervous system (CNS). Although several studies recently investigated the T-cell receptor (TCR) repertoire in cerebrospinal fluid (CSF) of MS patients by high-throughput sequencing (HTS), a deep analysis on repertoire similarities and differences among compartments is still missing. METHODS: We performed comprehensive bioinformatics on high-dimensional TCR Vβ sequencing data from published and unpublished MS and healthy donors (HD) studies. We evaluated repertoire polarization, clone distribution, shared CDR3 amino acid sequences (CDR3s-a.a.) across repertoires, clone overlap with public databases, and TCR similarity architecture. FINDINGS: CSF repertoires showed a significantly higher public clones percentage and sequence similarity compared to peripheral blood (PB). On the other hand, we failed to reject the null hypothesis that the repertoire polarization is the same between CSF and PB. One Primary-Progressive MS (PPMS) CSF repertoire differed from the others in terms of TCR similarity architecture. Cluster analysis splits MS from HD. INTERPRETATION: In MS patients, the presence of a physiological barrier, the blood-brain barrier, does not impact clone prevalence and distribution, but impacts public clones, indicating CSF as a more private site. We reported a high Vβ sequence similarity in the CSF-TCR architecture in one PPMS. If confirmed it may be an interesting insight into MS progressive inflammatory mechanisms. The clustering of MS repertoires from HD suggests that disease shapes the TCR Vβ clonal profile. FUNDING: This study was partly financially supported by the Italian Multiple Sclerosis Foundation (FISM), that contributed to Ballerini-DB data collection (grant #2015 R02)

Factors Influencing Vulnerability and Response to Ozone of the Vegetation at the Permanent Monitoring Plots of the CONECOFOR Programme in Italy.

Abstract not availableJRC.H-Institute for environment and sustainability (Ispra