How the intestinal tract develops a tolerance to foreign antigens is still largely unknown. Here we report that extracellular vesicles (EVs) with TGF-β1-dependent immunosuppressive activity are produced by intestinal epithelial cells (IECs) under physiological conditions. Transfer of these EVs into inflammatory bowel disease (IBD) mice induced by dextran sulfate sodium salt decreases IBD severity by inducing regulatory T cells and immunosuppressive dendritic cells. In contrast, decreased endogenous EV production promotes IBD development. IECs produce EVs with increased levels of TGF-β1 upon IBD development in an ERK-dependent manner. Furthermore, these EVs tend to localize in the intestinal tract associated with epithelial cell adhesion molecule (EpCAM). Knockdown of EpCAM in vivo increases the severity of murine IBD, and the protective effect of EVs from IECs with decreased EpCAM on murine IBD is blunted. Therefore, our study indicates that EVs from IECs participate in maintaining the intestinal tract immune balance.
Oral systemic antibiotics and mechanical bowel preparation significantly lowered the incidence of surgical site infection after elective colorectal surgery compared with systemic antibiotics alone and mechanical bowel preparation.
The incidence of lung cancer increases annually. However, the effects of the present methods for the treatment of lung cancer are extremely poor. It has been reported that exosomes from heat‑stressed 3LL Lewis lung tumor cells effectively elicit systemic antitumor immunity. CD40 signaling is critical in the activation of dendritic cells (DCs), which are important in the induction of antitumor immunity. In the present study, exosomes from CD40 ligand gene‑modified 3LL tumor cells (CD40L‑EXO) were identified to be more immunogenic compared with control‑EXO and lac Z-EXO. CD40L‑EXO induced a more mature phenotype of the DCs and promoted them to secrete high levels of interleukin‑12. CD40L‑EXO‑treated DCs induced a greater proliferation of allogeneic T cells in the mixed lymphocyte reaction. Moreover, CD40L‑EXO induced robust tumor antigen‑specific CD4+ T cell proliferation ex vivo. CD40L‑EXO were also extremely effective in the protective and therapeutic antitumor tests in vivo. These results indicate that CD40L‑EXO may be used as an efficient vaccine for lung cancer immunotherapy.
The TRAPPIST-1 system is a priority target for terrestrial exoplanet characterization. TRAPPIST-1e, residing in the habitable zone, will be observed during the JWST GTO Program. Here, we assess the prospects of differentiating between prebiotic and modern Earth scenarios for TRAPPIST-1e via transmission spectroscopy. Using updated TRAPPIST-1 stellar models from the Mega-MUSCLES survey, we compute self-consistent model atmospheres for a 1 bar prebiotic Earth scenario and two modern Earth scenarios (1 and 0.5 bar eroded atmosphere). Our modern and prebiotic high-resolution transmission spectra ($0.4 - 20\, {\rm \mu m}$ at R ∼100,000) are made available online. We conduct a Bayesian atmospheric retrieval analysis to ascertain the molecular detectability, abundance measurements, and temperature constraints achievable for both scenarios with JWST. We demonstrate that JWST can differentiate between our prebiotic and modern Earth scenarios within 20 NIRSpec Prism transits via CH4 abundance measurements. However, JWST will struggle to detect O3 for our modern Earth scenario to >2 σ confidence within the nominal mission lifetime (∼ 80 transits over 5 years). The agnostic combination of N2O and/or O3 offers better prospects, with a predicted detection significance of 2.7 σ with 100 Prism transits. We show that combining MIRI LRS transits with Prism data provides little improvement to atmospheric constraints compared to observing additional Prism transits. Though biosignatures will be challenging to detect for TRAPPIST-1e with JWST, the abundances for several important molecules – CO2, CH4, and H2O – can be measured to a precision of ≲ 0.7 dex (a factor of 5) within a 20 Prism transit JWST program.
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