Exosomes secreted from T cells have been shown to affect dendritic cells, cancer cells, and other T cells. However, little is known about how T-cell exosomes (T exosomes) modulate endothelial cell functions in the context of tissue-specific homing. Here, we study the roles of T exosomes in the regulation of gut-specific T-cell homing. The gut-tropic T cells induced by retinoic acid secrete the exosomes that upregulate integrin α4β7 binding to the MAdCAM-1 expressed on high endothelial venules in the gut. T exosomes were preferentially distributed to the villi of the small intestine in an α4β7-dependent manner. Exosomes from gut-tropic T cells suppressed the expression of MAdCAM-1 in the small intestine, thereby inhibiting T-cell homing to the gut. Moreover, microRNA (miRNA) profiling analysis has shown that exosomes from gut-tropic T cells were enriched with miRNAs targeting NKX2.3, a transcription factor critical to MAdCAM-1 expression. Taken together, our study proposes that α4β7-expressing T exosomes distribute themselves to the small intestine and modify the expression of microenvironmental tissues such that any subsequent lymphocyte homing is precluded. This may represent a novel mechanism by which excessive lymphocyte homing to the intestinal tissues is downsized.

Extracellular vesicles (EVs) in the plasma mediate important inter-cellular communications in the pathogenesis of cancer and inflammatory diseases. EVs express integrins that regulate target specificities and programed cell-1 ligand 1 and 2 (PD-L1 and 2) that suppress lymphocyte activation. However, the roles of these molecules on EVs in systemic inflammatory response syndrome (SIRS) and sepsis remain little understood. This study aimed to investigate how the EV expression of integrins and PD-1 ligands might differ in SIRS and sepsis, compared with healthy controls, and to correlate their expression with the clinical parameters reflecting pathogenesis. Twenty-seven SIRS patients without sepsis, 27 sepsis patients, and 18 healthy volunteers were included. EVs were isolated from plasma samples. The expression of three major integrins (β1, β2, β3 integrins) and PD-L1 and 2 were measured. The EV expression of β2 integrin and PD-L2 was significantly increased in sepsis patients compared with healthy controls. EV expression of PD-L1 was not elevated in sepsis and SIRS; however, circulating soluble PD-L1 levels were significantly higher in sepsis. Furthermore, EV expression of β2 integrin in sepsis patients correlated with hypotension and reduced kidney function. In addition, soluble PD-L1 levels correlated with sepsis severity, impaired kidney function, and impaired central nervous system function. These results suggest the potential involvements of the EV β2 integrin, as well as EV PD-L2 and soluble PD-L1, in the septic pathogenesis that occurs with the systemic immune activation leading to multiple organ dysfunctions.

e aril (mace) of Myristica fragrans, known as Dok-Chan, is a spice that has long been used for treating stomach discomfort, peptic ulcer, and nausea. It is an ingredient in many remedies in ai traditional medicine, e.g., Ya-Hom-ep-Bha-Jit, Ya-Hom-Nao-Wa-Kot, and Ya-at-Bun-Job, which are used to treat dyspepsia and other gastrointestinal tract symptoms. e aqueous and ethanolic extracts of mace were used for all tests. Anti-H. pylori activities were determined by the disc diffusion method and agar dilution. Anti-inflammatory activity was determined by the LPS-induced nitric oxide (NO) inhibition in a RAW264.7 cell line, and cytotoxicity was determined against gastric cancer cell lines (Kato III) using the sulphorhodamine B (SRB) assay. e DPPH radical scavenging and ABTS radical cation decolorization assays were used to determine the antioxidant activities. e result found that the ethanolic extract of mace exhibited antimicrobial activity against H. pylori ATCC 43504 and six clinical strains with MIC values of 125-250 μg/ml. e aqueous extract MICs against H. pylori ATCC reference strain and six clinical strains were 500 μg/ml compared with 0.5 μg/ml for the positive control, clarithromycin. e inhibitory effect of LPS-induced NO release and cytotoxic activity of the ethanolic extract had IC 50 values of 82.19 μg/ml and 26.06 μg/ml, respectively, and the EC 50 values for the DPPH and ABTS antioxidant assays were 13.41 μg/ml and 12.44 μg/ml, respectively. e mace extract also had anticancer properties. In conclusion, the ethanolic mace extract had anti-H. pylori, anti-inflammatory, antioxidant, and anticancer activities. ese data support further preclinical and clinical investigation to see if the mace extract could have a role in treating patients with dyspepsia, peptic ulcers, and possibly gastric cancer.

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