TIGIT can inhibit T cell activation via ligation-induced nanoclusters, independent of CD226 co-stimulation

TIGIT is an inhibitory receptor expressed on lymphocytes and can inhibit T cells by preventing CD226 co-stimulation through interactions in cis or through competition of shared ligands. Whether TIGIT directly delivers cell-intrinsic inhibitory signals in T cells remains unclear. Here we show, by analysing lymphocytes from matched human tumour and peripheral blood samples, that TIGIT and CD226 co-expression is rare on tumour-infiltrating lymphocytes. Using super-resolution microscopy and other techniques, we demonstrate that ligation with CD155 causes TIGIT to reorganise into dense nanoclusters, which coalesce with T cell receptor (TCR)-rich clusters at immune synapses. Functionally, this reduces cytokine secretion in a manner dependent on TIGIT’s intracellular ITT-like signalling motif. Thus, we provide evidence that TIGIT directly inhibits lymphocyte activation, acting independently of CD226, requiring intracellular signalling that is proximal to the TCR. Within the subset of tumours where TIGIT-expressing cells do not commonly co-express CD226, this will likely be the dominant mechanism of action

Bipyramidal anatase TiO₂ nanoparticles, a highly efficient photocatalyst? Towards a better understanding of the reactivity

International audienceAnatase nanoparticles with shape controlled bipyramidal morphology (TiO2-A-bipy) exhibited mainly {101} facets were synthesized through the sol–gel method and then used for the photodegradation of three model pollutants – Rhodamine B, phenol and formic acid – under UV-A radiation exposure. These titania samples exhibit better photocatalytic efficiency than the commercial TiO2-P25 reference for the dye degradation while this one demonstrates a higher activity for both phenol and formic acid. Moreover, supplementary washings of the particles significantly enhanced their photocatalytic efficiency in any case. To better understand these differences in term of photoactivity and the role of the TiO2 surface according to the nature of the targeted organic pollutant, various characterization techniques such as XRD, TEM and N2-sorption were used. Their surface properties were studied by FT-IR, TRMC and EPR. The presence of more acidic sites on TiO2-A-bipy surface could explain the faster degradation of the dye molecule through surface-mediated reactions. On the other side, a better generation and separation dynamic of photogenerated charges for TiO2-P25 could account for its higher photocatalytic efficiency for both formic acid and phenol degradation. This study shows that even if a quick test of dye degradation is mostly used in literature to confirm the efficiency of a photocatalyst, further investigation is often needed

Expression of SARS-CoV-2 Entry Molecules ACE2 and TMPRSS2 in the Gut of Patients With IBD

Patients with inflammatory bowel disease (IBD) have intestinal inflammation and are treated with immune-modulating medications. In the face of the coronavirus disease-19 pandemic, we do not know whether patients with IBD will be more susceptible to infection or disease. We hypothesized that the viral entry molecules angiotensin I converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are expressed in the intestine. We further hypothesized that their expression could be affected by inflammation or medication usage. We examined the expression of Ace2 and Tmprss2 by quantitative polymerase chain reacion in animal models of IBD. Publicly available data from organoids and mucosal biopsies from patients with IBD were examined for expression of ACE2 and TMPRSS2. We conducted RNA sequencing for CD11b-enriched cells and peripheral and lamina propria T-cells from well-annotated patient samples. ACE2 and TMPRSS2 were abundantly expressed in the ileum and colon and had high expression in intestinal epithelial cells. In animal models, inflammation led to downregulation of epithelial Ace2. Expression of ACE2 and TMPRSS2 was not increased in samples from patients with compared with those of control patients. In CD11b-enriched cells but not T-cells, the level of expression of ACE2 and TMPRSS2 in the mucosa was comparable to other functional mucosal genes and was not affected by inflammation. Anti-tumor necrosis factor drugs, vedolizumab, ustekinumab, and steroids were linked to significantly lower expression of ACE2 in CD11b-enriched cells. The viral entry molecules ACE2 and TMPRSS2 are expressed in the ileum and colon. Patients with IBD do not have higher expression during inflammation; medical therapy is associated with lower levels of ACE2. These data provide reassurance for patients with IBD

Understanding culture-led local development: A critique of alternative theoretical explanations

In this paper we carry out a meta-analytic review of the literature on culture-led local development models.We identify and discuss three typical fallacies characterising mono-causal culture-led development schemes: instrumentalism, over-engineering, and parochialism.We then discuss their analytical background, and provide examples illustrating the consequences of each. Based upon this critical discussion, we make a case for a ‘new territorial thinking’ approach that takes into account the tangled hierarchy of global and local viewpoints that is connatural to spatially situated cultural production, and focuses upon a non-linear, multi-causal scheme as the only possible framework for the policy design of credible, socially accountable, culture-led development strategie