TH17 cells express ST2 and are controlled by the alarmin IL-33 in the small intestine.

TH17 cells are major drivers of inflammation and involved in several autoimmune diseases. Tissue inflammation is a beneficial host response to infection, but it can also contribute to autoimmunity. The crosstalk between a tissue and the immune system during an inflammatory response is key for preserving tissue integrity and restoring physiological processes. However, how the inflamed tissue regulates the magnitude of an immune response by controlling pro-inflammatory T cells is not well characterized so far. Here we show that TH17 cells accumulating in the small intestine upon inflammation express the IL-33 receptor (ST2) and intestinal epithelial cells (IEC) are the main source of the alarmin interleukin-33 (IL-33). We show that pro-inflammatory TH17 cells acquire a regulatory phenotype with immunosuppressive properties in response to IL-33. Absence of ST2 signaling promotes the secretion of pro-inflammatory cytokines by TH17 cells and dampens the secretion of IL-10. Our results provide new insights into the mechanisms by which IEC, via IL-33/ST2 axis, may control pro-inflammatory TH17 cells in the small intestine to sustain homeostasis.

Efficacy of irrigation systems on penetration of sodium hypochlorite to working length and to simulated uninstrumented areas in oval shaped root canals.

AIM: To assess the ability of sodium hypochlorite (NaOCl) to penetrate simulated lateral canals and to reach working length (WL) when using the self-adjusting file (SAF). METHODOLOGY: Seventy single-rooted teeth with oval-shaped canals were used. Upon access, presence of a single canal was confirmed by direct visualization under a dental-operating microscope. Canal length and patency were obtained using a size 10 K-file and root length standardized to 18 mm. Pre-enlargement was restricted to the coronal one-third. The apical size of each canal was gauged at WL and samples larger than size 30 were excluded. Canals were instrumented for 5 min using the SAF system while delivering a total of 20 mL of 5.25% NaOCl and 5 mL of 17% EDTA. Then, the apical diameters were standardized to size 35 using hand files. Four hundred and twenty simulated lateral canals were then created during the clearing process and roots coated with wax to create a closed system. All samples were then cleared and randomly assigned to four experimental groups: 1 (n = 15) positive pressure; 2 (n = 15) SAF without pecking motion; 3 (n = 15) SAF with pecking motion; 4 (n = 15) apical negative pressure (ANP) irrigation and (n = 10) control groups. Samples were scored on the basis of the ability of the contrast solution to reach WL and permeate into the simulated lateral canals to at least 50% of the total length. The Kruskal-Wallis test was used to analyse irrigant penetration and the Tukey test to determine statistical differences between groups (P < 0.05). RESULTS: All samples irrigated with ANP were associated with irrigant penetration to WL (Table 1). The differences between group 4 (ANP) and all other groups were significant in penetration to WL (P < 0.05). The pecking motion allowed for further penetration of the irrigant when using the SAF system but failed to irrigate at WL. None of the experimental groups demonstrated predictable irrigation of simulated lateral canals. CONCLUSIONS: In this laboratory model, ANP was the only delivery system capable of irrigating consistently to full WL. None of the systems tested produced complete irrigation in artificial lateral canals.

CD84 functions as a homophilic adhesion molecule and enhances IFN-gamma secretion: adhesion is mediated by Ig-like domain 1.

CD84 is a member of the CD2 subset of the Ig superfamily of cell surface molecules. Its cytoplasmic tail binds to Src homology 2 domain-containing protein 1A (signaling lymphocytic activation molecule-associated protein), a protein encoded by the X-linked lymphoproliferative disease gene. It is preferentially expressed on B lymphocytes, monocytes, and platelets. We show that it is also expressed on thymocytes and T cells. CD84 was positive on CD4-CD8- thymocytes, and its expression decreased with cell maturation. It is expressed on mature T cells preferentially on CD45RO+. To identify the CD84 ligand, we generated a soluble Ig fusion protein containing the human CD84 extracellular domains (CD84-Ig). Because receptor-ligand interactions occur between several members of this subfamily, we assayed CD84-Ig binding with all members of the CD2 family. CD84-Ig bound to CD84-transfected cells, whereas no binding was detected with cells expressing other CD2 subfamily receptors, showing that CD84 binds to itself. Anti-CD84 mAbs recognizing epitopes wholly within domain 1 of CD84 blocked the binding of the CD84-Ig fusion protein to CD84-transfected cells and platelets. Data from CD84 domain human/mouse chimeras further revealed that only the first extracellular domain of the molecule is involved in the ligand receptor recognition. The CD84-CD84 interaction was independent of its cytoplasmic tail. Finally, concurrent ligation of human CD84 with mAbs or CD84-Ig and CD3 enhanced IFN-gamma secretion in human lymphocytes. Thus, CD84 is its own ligand and acts as a costimulatory molecule.

Technetium-99m tetrofosmin rest/stress myocardial SPET with a same-day 2-hour protocol: comparison with coronary angiography. A Spanish-Portuguese multicentre clinical trial.

Technetium-99m tetrofosmin (Myoview) has unique properties for myocardial perfusion imaging very early after injection of the tracer. We used a very short same-day rest/stress protocol, to be performed within 2 h and evaluated its diagnostic accuracy. The study included 144 patients from seven Spanish and four Portuguese centres with a diagnosis of uncomplicated coronary artery disease (CAD); 78 patients (54%) had no history of prior myocardial infarction. Patients were injected with /=50%) was achieved with a sensitivity of 64% for the left anterior descending artery, 49% for the left circumflex artery and 86% for the right coronary artery, and an accuracy of 71%, 72% and 73% respectively. Concordance of SPET and CA was 62% for single-vessel disease and 68% for multivessel disease. In conclusion, this Spanish-Portuguese multicentre clinical trial confirmed, in a considerable number of patients who underwent coronary angiography, the feasibility of 99mTc tetrofosmin (Myoview) rest/stress myocardial SPET using a very short protocol (2 h).

Systolic compression of coronary artery in hypertrophic cardiomyopathy.

To determine the prevalence and significance of the systolic compression of the anterior descending coronary artery in hypertrophic cardiomyopathy, we studied 54 consecutive patients out of a catheterization laboratory population of 1619. This angiographic finding was found to be more prevalent (P less than 0.001) and severe in myopathic than in secondary hypertrophy. Complete systolic occlusion occurred in 5 of the 6 patients with nonobstructive cardiomyopathy showing the systolic narrowing. Severe septal squeezing was also present in these cases and the diastolic time lag to refill the distal branches reached 20-33% of the diastolic period. This subset of patients showed the least dynamic anterior wall contraction (P less than 0.001) and the highest incidence of thallium-201 perfusion defects (P less than 0.05) and of recurrent cardiac arrest (P less than 0.05). We conclude that severe systolic compression of the descending coronary artery in hypertrophic cardiomyopathy may be an angiographic marker of the myopathic hypertrophy extending to the anterior wall and might contribute to ischemia when the time to restore the distal perfusion is greatly delayed.