Mucosa-associated invariant T cells link intestinal immunity with antibacterial immune defects in alcoholic liver disease

Background/aims: Intestinal permeability with systemic distribution of bacterial products are central in the immunopathogenesis of alcoholic liver disease (ALD), yet links with intestinal immunity remain elusive. Mucosa-associated invariant T cells (MAIT) are found in liver, blood and intestinal mucosa and are a key component of antibacterial host defences. Their role in ALD is unknown. Methods/design: We analysed frequency, phenotype, transcriptional regulation and function of blood MAIT cells in severe alcoholic hepatitis (SAH), alcohol-related cirrhosis (ARC) and healthy controls (HC). We also examined direct impact of ethanol, bacterial products from faecal extracts and antigenic hyperstimulation on MAIT cell functionality. Presence of MAIT cells in colon and liver was assessed by quantitative PCR and immunohistochemistry/gene expression respectively. Results: In ARC and SAH, blood MAIT cells were dramatically depleted, hyperactivated and displayed defective antibacterial cytokine/cytotoxic responses. These correlated with suppression of lineage-specific transcription factors and hyperexpression of homing receptors in the liver with intrahepatic preservation of MAIT cells in ALD. These alterations were stronger in SAH, where surrogate markers of bacterial infection and microbial translocation were higher than ARC. Ethanol exposure in vitro, in vivo alcohol withdrawal and treatment with Escherichia coli had no effect on MAIT cell frequencies, whereas exposure to faecal bacteria/antigens induced functional impairments comparable with blood MAIT cells from ALD and significant MAIT cell depletion, which was not observed in other T cell compartments. Conclusions: In ALD, the antibacterial potency of MAIT cells is compromised as a consequence of contact with microbial products and microbiota, suggesting that the ‘leaky’ gut observed in ALD drives MAIT cell dysfunction and susceptibility to infection in these patients

Bilateral cauliflower ear deformity: An unusual presentation of cutaneous Rosai-Dorfman disease

10.1097/01.PRS.0000105646.49729.3FPlastic and Reconstructive Surgery1133967-969PRSU

Measurement of the BB−^{-} →\rightarrow DD0^{0}ℓ\ell−^{-}νˉ\bar{\nu}ℓ_{\ell} Branching Fraction in 62.8 fb−1^{-1} of Belle II data

We report a measurement of the branching fraction of the semileptonic decay $B$$^{-}$ $\rightarrow$ $D$$^{0}$$\ell$$^{-}$$\bar{\nu}$$_{\ell}$ (and its charge conjugate) using 62.8 fb$^{-1}$ of $\Upsilon$(4$S$) $\rightarrow$ $B$$\bar{B}$ data recorded by the Belle II experiment at the SuperKEKB asymmetric-energy $e$$^{+}$ $e$$^{-}$ collider. The neutral charm meson is searched for in the decay mode $D$$^{0}$ $\rightarrow$ $K$$^{-}$ $\pi$$^{+}$ and combined with a properly charged identified lepton (electron or muon) to reconstruct this decay. No reconstruction of the second $B$ meson in the $\Upsilon$(4$S$) event is performed. We obtain $B$($D$$^{0}$$\ell$$^{-}$$\bar{\nu}$$_{\ell}$) = (2.29 $\pm$ 0.05 $_{stat}$ $\pm$ 0.08$_{syst}$, in agreement with the world average of this decay. We also determine the ratio of the electron to muon branching fractions to be $R$($e$/$\mu$) = 1.04 $\pm$ 0.05$_{stat}$ $\pm$ 0.03$_{syst}$ and observe no deviation from lepton universality

Measurement of the BB−^{-} →\rightarrow DD0^{0}ℓ\ell−^{-}νˉ\bar{\nu}ℓ_{\ell} Branching Fraction in 62.8 fb−1^{-1} of Belle II data

We report a measurement of the branching fraction of the semileptonic decay $B$$^{-}$ $\rightarrow$ $D$$^{0}$$\ell$$^{-}$$\bar{\nu}$$_{\ell}$ (and its charge conjugate) using 62.8 fb$^{-1}$ of $\Upsilon$(4$S$) $\rightarrow$ $B$$\bar{B}$ data recorded by the Belle II experiment at the SuperKEKB asymmetric-energy $e$$^{+}$ $e$$^{-}$ collider. The neutral charm meson is searched for in the decay mode $D$$^{0}$ $\rightarrow$ $K$$^{-}$ $\pi$$^{+}$ and combined with a properly charged identified lepton (electron or muon) to reconstruct this decay. No reconstruction of the second $B$ meson in the $\Upsilon$(4$S$) event is performed. We obtain $B$($D$$^{0}$$\ell$$^{-}$$\bar{\nu}$$_{\ell}$) = (2.29 $\pm$ 0.05 $_{stat}$ $\pm$ 0.08$_{syst}$, in agreement with the world average of this decay. We also determine the ratio of the electron to muon branching fractions to be $R$($e$/$\mu$) = 1.04 $\pm$ 0.05$_{stat}$ $\pm$ 0.03$_{syst}$ and observe no deviation from lepton universality