SummaryInflammatory bowel diseases are characterized by a deregulated immune response targeting the gut bacterial flora. Mucosal-associated invariant T (MAIT) cells are major histocompatibility complex (MHC) class Ib-restricted innate-like lymphocytes with anti-bacterial functions. They display an effector/memory phenotype and are found in large numbers in the blood, mucosae and liver. They have also been implicated in inflammatory diseases such as multiple sclerosis. Therefore, we aimed to analyse the possible involvement of MAIT cells in Crohn's disease (CD) and ulcerative colitis (UC). To this end, a phenotypical and functional analysis of MAIT cells isolated from the blood of healthy subjects, CD and UC patients was undertaken. MAIT cells were also quantified in ileal biopsies of CD patients. The frequency of blood MAIT cells was specifically reduced in IBD patients compared with healthy donors, whereas it was dramatically greater in the inflamed versus healthy tissue. MAIT cells were activated as they expressed significantly more the Ki67 antigen, and this was accompanied by phenotypical changes such as increased expression of natural killer (NK)G2D and B and T lymphocyte attenuator (BTLA). Finally, in-vitroactivated MAIT cells from CD and UC patients secreted significantly more interleukin (IL)-17, together with a decreased interferon (IFN)-γ in CD but an increased IL-22 in UC. These data show that MAIT cells are activated in IBD, which results in an increased recruitment towards the inflamed tissues, an altered phenotype and a switch in the pattern of cytokine secretion. This is the first demonstration that MAIT cells are immune players in IBD, whose precise functions in this context need to be addressed.

Although combination therapy with prednisolone plus N-acetylcysteine increased 1-month survival among patients with severe acute alcoholic hepatitis, 6-month survival, the primary outcome, was not improved. (Funded by Programme Hospitalier de Recherche Clinique; AAH-NAC ClinicalTrials.gov number, NCT00863785 .).

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SUMMARY Background

Most GCA-positive TAs contained VZV in skip areas that correlated with adjacent GCA pathology, supporting the hypothesis that VZV triggers GCA immunopathology. Antiviral treatment may confer additional benefit to patients with GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive forms of cancer with a tendency to invade surrounding healthy tissues, leading to a largely incurable disease. Despite many advances in modern medicine, there is still a lack of early biomarkers as well as efficient therapeutical strategies. The melastatin-related transient receptor potential 7 channel (TRPM7) is a nonselective cation channel that is involved in maintaining Ca 21 and Mg 21 homeostasis. It has been recently reported to regulate cell differentiation, proliferation and migration. However, the role of TRPM7 in PDAC progression is far to be understood. In our study, we show that TRPM7 is 13-fold overexpressed in cancer tissues compared to the healthy ones. Furthermore, TRPM7 staining is stronger in tumors with high grade, suggesting a correlation between TRPM7 expression and PDAC progression. Importantly, TRPM7 expression is inversely related to patient survival. In BxPC-3 cell line, dialyzing the cytoplasm during the patch-clamp whole-cell recording with a 0-Mg 21 solution activated a nonselective current with a strong outward rectification. This cation current is inhibited by intracellular Mg 21 and by TRPM7 silencing. The downregulation of TRPM7 by small interference RNA dramatically inhibited intracellular Mg 21 fluorescence and cell migration without affecting cell proliferation, suggesting that TRPM7 contributes to Mg 21 entry and cell migration. Moreover, external Mg 21 following TRPM7 silencing fully restored the cell migration. In summary, our results indicate that TRPM7 is involved in the BxPC-3 cell migration via a Mg 21 -dependent mechanism and may be a potential biomarker of poor prognosis of PDAC.Pancreatic ductal adenocarcinoma (PDAC) is the fifth most frequent cause of cancer-related mortality in the European Union 1 and the the fourth most frequent cause in the United States. 2 PDAC has a poor long-term prognosis with 5-year survival rates of only 1-4%. Current therapeutic strategies generally result in only a few months of extended life because PDAC develops insidiously and metastasizes quickly and widely. Thus, a greater understanding of the molecular processes involved in PDAC progression and metastasis is urgently needed.Ion channels are transmembrane proteins that are involved in a wide panel of physiological cell mechanisms, including excitability, secretion, proliferation, apoptosis and motility. Nevertheless, a growing amount of studies show that ion channels expression is altered in several cancers including breast and prostate. 3 Among these ion channels, members of the transient receptor potential (TRP) family have been proposed as prognosis markers in breast and prostate cancers. 4,5 TRP melastatin-related 7 (TRPM7) channels are a member of ''chanzymes,'' which are unique feature of cation channels fused with a kinase function. 6,7 They allow magnesium and calcium entries; however, they are mainly involved in magnesium homeostasis. 8 In the digestive system, TRPM7 channels are expressed and involved in ...

The infiltration of tumors by lymphocytes is a prognosis factor in colorectal cancer (CRC). The magnitude and quality of this infiltration have emerged as important component of the clinical outcome in these patients. Specifically, markers associated with functional cell-mediated immunity, i.e., a Th1 immune response, are independent markers of better prognosis, whereas Th17-associated components are deleterious and correlate with poorer survival. Mucosal-associated invariant T (MAIT) cells are a recently described T cell subset with tissue-homing properties. They display a restricted TCR repertoire specific for widely conserved microbial ligands, and display anti-bacterial properties upon release of Th1-like, Th17-like, and/or cytotoxic granules. MAIT-cell-specific transcripts have been found in kidney and brain cancer, but have not been studies in other sites. In this study, we retrospectively analyzed by confocal microscopy the presence of MAIT cells within colorectal tumors as compared with paired healthy tissues. We observed a significant although variable increase, both in density and in proportion of overall tumor-infiltrating T lymphocytes inside the tumors. Importantly, survival curves as well as multivariate analysis showed that patients displaying a higher recruitment of MAIT cells in their tumor, as compared with the neighboring healthy tissue, showed a less favorable clinical outcome. This study suggests that including MAIT-cell-specific markers or transcripts in the analysis of tumor-infiltrating lymphocytes could be a benefit to the diagnosis and follow-up of CRC patients.

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