Immunology of the Gut

Special AT-rich sequence binding protein 1 (SATB1) is a genome organizer that is expressed by T cells. T cell development is severely impaired in SATB1 null mice; however, because SATB1 null mice die by 3 wk of age, the roles of SATB1 in T cell development have not been well clarified. In this study, we generated and analyzed SATB1 conditional knockout (cKO) mice, in which the SATB1 gene was deleted from all hematopoietic cells. T cell numbers were reduced in these mice, mainly because of a deficiency in positive selection at the CD4(+)CD8(+) double-positive stage during T cell development in the thymus. We also found that SATB1 cKO mice developed autoimmune diseases within 16 wk after birth. In SATB1 cKO mice, the numbers of Foxp3(+) regulatory T (Treg) cells were significantly reduced at 2 wk of age compared with wild-type littermates. Although the numbers gradually increased upon aging, Treg cells in SATB1 cKO mice were still less than those in wild-type littermates at adulthood....

To analyze the effect of IL-10 overexpressed by APCs as observed in some SCID patients, we have expressed the human IL-10 cDNA under the control of the murine MHC class II promoter in transgenic mice. Similar to SCID patients, these mice presented a defect in T cell maturation characterized by a rapid thymic aplasia that started after birth. The blockage in T cell maturation was strictly restricted to TCR-alpha beta T cells as the absolute number of thymic dendritic, TCR-gamma delta and NK1.1 T cells were equivalent to control littermates. Crossing IL-10 transgenic mice with TCR transgenic mice or treatment with staphylococcal enterotoxin B showed that the defect was not related to the impairment of positive or negative selection. However, repopulating of IL-10 transgenic mouse-fetal thymic organ culture with different stages of triple negative T cells isolated from control mice showed that the blockage occurred specifically at the pre-T cell stage and was reverted by treatment with...

Certain inflammatory cytokines and growth factors have been previously shown to interact with glycosaminoglycan moieties of the extracellular matrix (ECM). We have examined the association of the pleiotropic cytokine TNF-alpha with glycoprotein constituents of ECM. TNF-alpha interacted with fibronectin (FN) and laminin, and to a lesser degree with collagen. The major binding site for TNF-alpha on FN was localized to its 30-kDa N-terminal fragment (FN-N') with a Ki in the sub-nM range. The binding of 125I-labeled TNF-alpha to immobilized FN or FN-N' persisted for at least 24 h, and was specifically inhibited by antibodies to FN, mAb directed against the FN-N' domain, unlabeled TNF-alpha, and by the truncated forms of TNF-alpha receptors. Once bound to immobilized FN or FN-N', the cytokine could not be released by the soluble TNF-alpha-receptors, although it could be released by anti-TNF-alpha Ab. TNF-alpha was also found to interact with soluble FN, although with a lo...

Dietary fiber (DF) was considered an antinutritional factor due to its adverse effects on feed intake and nutrient digestibility. However, with increasing evidence, scientists have found that DF has enormous impacts on the gastrointestinal tract (GIT) development, digestive physiology, including nutrient digestion, fermentation, and absorption processes of poultry. It may help maintain the small and large intestine's integrity by strengthening mucosal structure and functions and increasing the population and diversity of commensal bacteria in the GIT. Increasing DF content benefits digestive physiology by stimulating GIT development and enzyme production. And the inclusion of fiber at a moderate level in diets also alters poultry growth performance. It improves gut health by modulating beneficial microbiota in the large intestine and enhancing immune functions. However, determining the source, type, form, and level of DF inclusion is of utmost importance to achieve the above-noted benefits. This paper critically reviews the available information on dietary fibers used in poultry and their effects on nutrient utilization, GIT development, gut health, and poultry performance. Understanding these functions will help develop nutrition programs using proper DF at an appropriate inclusion level that will ultimately lead to enhanced DF utilization, overall health, and improved poultry growth performance. Thus, this review will help researchers and industry identify the sources, type, form, and amount of DF to be used in poultry nutrition for healthy, cost-effective, and eco-friendly poultry production.

Ο όρος ιδιοπαθείς φλεγμονώδεις νόσοι του εντέρου (ΙΦΝΕ) αναφέρεται σε δύο διακριτές νόσους που χαρακτηρίζονται από την παρουσία οξείας και χρόνιας φλεγμονής: στην ελκώδη κολίτιδα και τη νόσο Crohn. Τις τελευταίες δεκαετίες, καταγράφεται αυξανόμενη επίπτωση και επιπολασμός της ελκώδους κολίτιδας και της νόσου Crohn κυρίως στις χώρες της Βόρειας Ευρώπης και Βόρειας Αμερικής. H εξέλιξη και χρήση καινοτόμων φαρμακευτικών ουσιών έχουν αλλάξει την πρόγνωση των ΙΦΝΕ. Παρ’ όλα αυτά συνεχίζει να υφίσταται η ανάγκη εύρεσης συμπληρωματικών θεραπευτικών προσεγγίσεων χαμηλού ρίσκου. Στο πλαίσιο αυτό αξιολογήθηκε η δράση συμπληρώματος Μαστίχας Χίου σε ασθενείς σε έξαρση και ύφεση των ΙΦΝΕ. Συγκεκριμένα αξιολογήθηκαν τα επίπεδα των IgG (ASCAs) σε ασθενείς με ελκώδη κολίτιδα, νόσο του Crohn αλλά και σε υγιείς συμμετέχοντες καθώς και η συσχέτιση των επιπέδων IgG (ASCAs) με βιοχημικούς δείκτες, δείκτες ενεργότητας και δείκτες φλεγμονής-οξείδωσης. Τέλος, ελέγχθηκε η επίδραση σκευάσματος Μαστίχας Χίου στα επίπεδα των αντισωμάτων IgG (ASCAs) σε ασθενείς σε έξαρση και ύφεση της νόσου Crohn, σε σχέση με εικονικό φάρμακο. Τα αποτελέσματα κατέδειξαν μια σαφή διαφορά ανάμεσα στα επίπεδα των αντισωμάτων σε υγιείς, ασθενείς με ελκώδη κολίτιδα και νόσο Crohn με τους ασθενείς με νόσο Crohn να παρουσιάζουν υψηλότερα επίπεδα αντισωμάτων σε σχέση με τις άλλες δυο ομάδες. Η συσχέτιση που καταγράφηκε μεταξύ των επιπέδων των αντισωμάτων με τους δείκτες ενεργότητας (Harvey-Bradshaw, Mayo, IBDQ) και τους δείκτες φλεγμονής-οξείδωσης (CRP, IL-6, IL-10, Lagtime, oxLDL) δεν είναι στατιστικά σημαντική. Κατά τον έλεγχο της συσχέτισης των επιπέδων των αντισωμάτων με μια σειρά βιοχημικών δεικτών, καταγράφηκε στατιστικά σημαντική (p<0.05) αρνητική συσχέτιση για τους βιοχημικούς δείκτες σίδηρος, ολική χοληστερόλη, LDL χοληστερόλη και αλβουμίνη. H επίδραση σκευάσματος Μαστίχας Χίου στα επίπεδα των αντισωμάτων IgG (ASCAs) σε ασθενείς σε έξαρση και ύφεση της νόσου Crohn, σε σχέση με εικονικό φάρμακο δεν απέφερε κάποιο στατιστικά σημαντικό αποτέλεσμα. Τα αποτελέσματα επιβεβαιώνουν τη διαγνωστική αξία των επιπέδων των αντισωμάτων IgG (ASCAs) ως διαγνωστικού δείκτη για τις ΙΦΝΕ αλλά και ως δείκτη που μπορεί να επιτρέψει τη διάκριση μεταξύ νόσου Crohn και ελκώδους κολίτιδας. Τέλος, αξίζει να διερευνηθεί σε μεγαλύτερο βαθμό η χρήση των επιπέδων IgG (ASCAs) σε συνδυασμό με τα επίπεδα σιδήρου σε ασθενείς με ΙΦΝΕ ως προγνωστικών δεικτών.

Λέξεις κλειδιά : Iδιοπαθείς Φλεγμονώδεις Νόσοι του Εντέρου, Ελκώδη κολίτιδα, νόσος Crohn, IgG (ASCAs), Μαστίχα Χίου, δείκτες ενεργότητας, διαγνωστικοί δείκτες, αυτοαντισώματα 

Abstract
The term Inflammatory Bowel Disease refers to two distinct diseases that are characterized by the presence of acute and chronic inflammation: ulcerative colitis and Crohn disease. During the last decades an increased incidence and prevalence of IBD diseases has been noted mainly in North America and Northern Europe. The prognosis of IBD has been affected by the introduction of novel drugs. However, there is still a need for new complementary low-risk therapeutic approaches. To this end, the effect of natural Mastic supplement was evaluated in patients with exacerbation and remission of IBD. More specifically, the levels of IgG (ASCAs) antibodies were evaluated in patients with ulcerative colitis, Crohn disease and in healthy individuals along with the correlation of ASCAs levels with certain biochemical markers, disease activity indexes and oxidation-inflammation biomarkers. Lastly, the effect of Mastiha supplement on ASCAs levels in patients with exacerbation and remission of Crohn disease was assessed. The results depict a difference between the ASCAs levels among healthy individuals, patients with ulcerative colitis and patients with Crohn disease, with the latter having higher levels compared to the two other groups. Correlation between ASCAs levels and Disease Activity Indexes (Harvey-Bradshaw, Mayo, IBDQ) as well as between ASCAs levels and oxidation-inflammation biomarkers (CRP, IL-6, IL-10, Lagtime, oxLDL) is statistically insignificant. However, a statistically significant negative correlation was noted when levels of ASCAs were correlated with certain biochemical markers (Fe, total cholesterol, LDL cholesterol, albumin). The Mastiha supplement did not have any significant effect on the ASCAs levels of patients with exacerbation and remission of Crohn disease, compared to a placebo drug. These results bring out the diagnostic value of ASCAs as a diagnostic marker for IBD along with its ability to distinguish between cases of ulcerative colitis and Crohn’s disease. The results also indicate the possibility of using the ASCAs levels in combination with serum Fe levels as prognostic markers in IBD. 

Keywords: Idiopathic inflammatory bowel diseases, Ulcerative colitis, Crohn's disease, IgG (ASCAs), Mastiha, activity markers, diagnostic markers, autoantibodies

This study compared the efficacy of Pe-diococcus acidilactici, mannan-oligosaccharide, butyric acid, and their combination on growth performance and intestinal health in broiler chickens challenged with S. Typhimurium. Ross 308 male broilers (n = 420) were randomly assigned to one of the 6 treatments , resulting in 5 replicate pens of 14 chicks per treatment. The treatments included a negative control [(NC), no additive, not challenged]; positive control [(PC), no additive, but challenged with S. Ty-phimurium at d 3 posthatch], and 4 groups whereby birds were challenged with S. Typhimurium at d 3 posthatch and fed diets supplemented with either pro-biotic [0.1 g/kg Pediococcus acidilactici (PA)], prebi-otic [2 g/kg mannan-oligosaccharides (MOS)], organic acid [0.5 g/kg butyric acid (BA)], or a combination of the 3 additives (MA). The S. Typhimurium challenge decreased feed intake, body weight gain and increased feed conversion ratio and reduced jejunum vil-lus height (VH) and VH to crypt depth (CD) ratio (P < 0.05). Birds on the MA treatment exhibited similar performance to birds on the NC treatment (P > 0.05) and had a lower population of Salmonella in the ceca compared with birds on the PC treatment, at d 14 and 21 post-challenge (P < 0.05). The lowest heterophil to lymphocyte ratio was observed in birds on the MA and NC treatments (P < 0.05). Birds fed diets supplemented with MA or PA had greater VH and VH: CD ratio than birds on the PC treatment at d 7, 14 and 21 d post-challenge (P < 0.05). Suppressed amylase and protease activity was observed as a result of the S. Typhimurium challenge; the enzyme levels were restored in birds fed the additive-supplemented diets, when compared to the birds on the PC treatment , particularly at d 21 post-challenge (P < 0.05). These results indicate that dietary supplementation with a combination of PA, BA, and MOS in broiler chickens could be used as an effective tool for controlling S. Typhimurium and promoting growth performance .

Arthritis in a genetically susceptible SKG strain of mice models a theoretical paradigm wherein autoimmune arthritis arises because of interplay between preexisting autoreactive T cells and environmental stimuli. SKG mice have a point mutation in ZAP-70 that results in attenuated TCR signaling, altered thymic selection, and spontaneous production of autoreactive T cells that cause arthritis following exposure to microbial β-glucans. In this study, we identify Nod2, an innate immune receptor, as a critical suppressor of arthritis in SKG mice. SKG mice deficient in Nod2 (Nod2SKG) developed a dramatically exacerbated form of arthritis, which was independent of sex and microbiota, but required the mutation in T cells. Worsened arthritis in Nod2SKG mice was accompanied by expansion of Th17 cells, which to some measure coproduced TNF, GM-CSF, and IL-22, along with elevated IL-17A levels within joint synovial fluid. Importantly, neutralization of IL-17A mitigated arthritis in Nod2SKG mice,...

Ryo Abe Toru Abo David Abraham Edward Abraham Kristin Abraham Lawrence Abraham Soman Abraham Scott Abrams Steven Abramson Maria Abreu-Marti Sergio Abrignani Roberto Accolla Hans Acha-Orbea Oreste Acuto David Adams Gosse Adema Minou Adib-Conquy Rebecca Adkins Adam Adler Luciano Adorini Bharat Aggarwal Carlo Agostini Alok Agrawal Devendra Agrawal Hector Aguila Karen Aguirre Adriano Aguzzi Joseph Ahearn A. Ahmed S. Ahmed Setsuya Aiba Iannis Aifantis Arne Akbar Shizuo Akira Mustufa Akkoyunlu Pradip Akolkar Salvatore Albani Steven Albelda Gottfried Alber Jose Alberola-Ila Jorge Albina Andres Alcover Carla Jo Aldrich Maria-Luisa Alegre Martha Alexander-Miller Lena Al-Harthi Hydar Ali Julio Aliberti Paola Allavena Judith Allen Paul Allen Todd Allen James Allison Janette Allison Gunnar Alm Francesca Aloisi Frederick Alt John Altman Daniel Altmann Richard Ambinder Julian Ambrus Sebastian Amigorena Ashok Amin Yassine Amrani Claudio Anasetti Peter Andersen Clark Anderson David Anderson Kenneth...