BackgroundEven though thymic stromal lymphopoietin (TSLP) has been implicated in the development of allergic inflammation, its influence on immune tolerance mediated by regulatory T cells (Treg) have not been explored. We aimed to dissect the influence of TSLP on immunosuppressive activities of Treg and its potential consequences in human allergic asthma.MethodsIn vitro culture system was utilized to study the effects of TSLP on human Treg. The functional competency of pulmonary Treg from a cohort of 15 allergic asthmatic, 15 healthy control, and 15 non-allergic asthmatic subjects was also evaluated by suppression assays and flow cytometric analysis.ResultsActivated pulmonary Treg expressed TSLP-R and responded to TSLP-mediated activation of STAT5. TSLP directly and selectively impaired IL-10 production of Treg and inhibited their suppressive activity. In human allergic asthma, pulmonary Treg exhibited a significant decrease in suppressive activity and IL-10 production compared to healthy control and non-allergic asthmatic counterparts. These functional alterations were associated with elevated TSLP expression in bronchoaveolar lavage fluid (BAL) of allergic asthmatic subjects. Furthermore, allergic asthmatic BAL could suppress IL-10 production by healthy control pulmonary Treg in a TSLP-dependent manner.ConclusionsThese results provide the first evidences for a direct role of TSLP in the regulation of suppressive activities of Treg. TSLP mediated inhibition of Treg function might present a novel pathologic mechanism to dampen tolerogenic immune responses in inflamed asthmatic airway.

Background CD4+CD25hiCD127lo/− regulatory T cells have been suggested to be critical regulators of inflammatory processes in allergic asthma. Recent studies reported a selective decrease in the frequency of regulatory T cells in the bronchoalveolar lavage fluid of allergic asthmatic (AA) subjects, prompting the possibility of defective recruitment of these cells to the airway in response to chemokines produced during asthmatic inflammation. Objectives This study aimed to characterize the chemotactic profile of circulating regulatory T cells in AA subjects in response to chemokines abundantly produced in airway inflammation, such as CCL1, CCL17, and CCL22. Methods The study was performed in a cohort of 26 AA, 16 healthy control, and 16 non-AA subjects. We used chemotaxis assays to evaluate cell migration, flow cytometry to examine chemokine receptor expression, and phospho-ELISA to study consequent signaling pathways in regulatory T cells. Results Regulatory T cells, but not CD4+CD25−T cells, from AA subjects showed decreased chemotactic responses, specifically to CCL1, in comparison with their healthy control and non-AA counterparts. Decreased CCL1-mediated chemotaxis in AA regulatory T cells was associated with decreased phosphorylation of protein kinase B (AKT), a protein involved in chemokine intracellular signaling. Furthermore, the decreased chemotactic response to CCL1 in AA regulatory T cells significantly correlated with asthma severity and decreased pulmonary function in AA subjects. Conclusions These results provide the first evidence of dysfunction in the chemokine signaling pathway in AA regulatory T cells.

Background— Antithymocyte globulin (ATG) is used as induction therapy after cardiac transplant for enhancing immunosuppression and delaying the initiation of nephrotoxic drugs. It is unknown if ATG induction is associated with decreased coronary plaque progression by intravascular ultrasound (IVUS). Methods and Results— Patients transplanted between March 2010 and December 2012 with baseline and 1-year IVUS were included. All patients transplanted were included in a secondary analysis. Change in plaque progression was measured in a blinded fashion on matched coronary segments and contrasted between patients induced with ATG and those who were not. One hundred and three patients were included in IVUS arms. Mean age at transplant was 55.8±12.6 years, and 33.0% were female. Patients induced with ATG were more sensitized (54.3% versus 14.3%). Plaque progression was attenuated in patients who received ATG by changes in maximal intimal area (1.0±1.2 versus 2.3±2.6 mm 2 ; P =0.001), maximal percent stenosis (6.3±7.9 versus 12.8±12.3%; =0.003), maximal intimal thickness (0.2±0.2 versus 0.3±0.3 mm; P =0.035), and plaque volume (0.5±0.7 versus 1.0±1.3 mm 3 /mm; P =0.016). Rapid plaque progression by maximal percent stenosis (≥20%) occurred less frequently in the ATG arm (4.3% versus 26.3; P =0.003). Survival ( P =0.242) and any treated rejection ( P =0.166) were not statistically different between groups. Patients receiving ATG had a higher rate of first-year infection ( P =0.003), perhaps related to increased intravenous antibiotic use immediately postoperatively, and a trend toward more biopsy-proven rejection ( P =0.073). Conclusions— Induction therapy with ATG is associated with reduced first-year coronary plaque progression as assessed by IVUS, despite an increased prevalence of sensitized patients with a trend toward more rejection.

PCI strategy using EES in the treatment of CAV was associated with a low binary restenosis rate, a high survival rate, and a high rate of freedom from MACE. However, at 3 years, TLR and TVR rates appeared similar to rates observed with first-generation DES. © 2016 Wiley Periodicals, Inc.

control subjects. THP was isolated from urine samples of 23 patients with IC and 24 control subjects by salt precipitation. The sialic acid contents were measured using 1,2-diamino-4,5-methylene dioxybenzenehigh performance liquid chromatography analysis. For N-glycan profiling, purified THP was treated with peptide:N-glycosidase F to release N-glycans. The purified N-glycans were labelled with 2-aminobenzamide and were profiled by high-pH anion exchange chromatography (HPAEC) with fluorescence detection. The neutral and amino sugars were determined by HPAEC with pulsed amperometric detection. RESULTSThe total sialic acid in patients was half of that in controls. There was a pattern of reduced level of high molecular weight sialylated oligosaccharide in 17 of 23 patients vs four of 24 controls. The total neutral and amino sugars showed a ≈ 30% reduction in patients. The mean ( SEM ) for the controls was 133.79 (6.51) vs 94.76 (6.67) nmol/200 µ g of THP for patients ( P < 0.001). CONCLUSIONSTHP in patients with IC has reduced sialylation and overall glycosylation, and by inference, THP has a role in the pathophysiology of IC. KEYWORDS Tamm-Horsfall protein, interstitial cystitis, glycosylationStudy Type -Aetiology (case series) Level of Evidence 4 OBJECTIVETo confirm abnormal glycosylation of TammHorsfall protein (THP) in patients with interstitial cystitis (IC). PATIENTS, SUBJECTS AND METHODSThe sialic acid content of THP, a critical component of its biological activity, is reduced in patients with IC. N-glycan shows reduced levels of high molecular weight tri-and tetra-antennary sialylated oligosaccharides. These results are supported by quantitative monosaccharide analysis of neutral and amino sugars in patients vs