Muc5ac Expression Protects the Colonic Barrier in Experimental Colitis

Abstract included in the text

Perspectives and Practices of the Staff of an Irish Post-Primary School in Addressing the Needs of Exceptionally Able Pupils

Given the dearth of research in relation to exceptionally able pupils in Ireland, the aim of this study was to add to the literature by way of further understand the ways in which these pupils are viewed, and how they are identified and provision is made for them. As a duel exceptional learner myself (one who is both intellectually gifted and disabled) I’ve been fascinated by society’s delight in pathologising difference, and the cost that is accrued not only by the individuals mislabelled, but to society as a whole. In every school classroom throughout Ireland there is likely a cohort of exceptionally able pupils who need opportunities to maximise their potential. Of this group, between 1/5 and 1/6 of them are also disabled. In Ireland, exceptionally able pupils are included under the category of pupils with special educational needs in the 1998 Education Act, while The Education for Persons with Special Educational Needs (EPSEN) Act, 2004, does not explicitly refer to such needs and the Exceptionally Able Students Guidelines for Teachers have remained in draft form since they were published in 2007. Given this confusing and contradictory landscape it is unsurprising that many schools do not have a formal system of identifying exceptionally able students and the aim of this study was to find out what was happening in one post-primary school in Ireland. First, a specially designed questionnaire was sent to every member of staff of the school with either teaching or care responsibility of these pupils in order to get a broad outline of how staff in the school conceptualise exceptional ability, and how they identify and make provision for exceptionally able pupils. This is followed by an in-depth examination of the main issues with five members of staff who volunteered to participate in one to one interviews. The findings from the interviews expanded (sometimes contradicted) the findings from questionnaire as participants report on their day-to-day experience of interaction with this cohort of students. In general, the staff were supportive of providing support for the students, however on a practical level this support was ad hoc and hampered by an uncertainty as to what constituted an exceptionally able pupil. In particular, the egalitarian educational outlook prevalent in Irish schools places an emphasis on pupils with learning difficulties and raising their test scores with little or no emphasis on ensuring the exceptionally able reach their full potential. Finally, staff reported a requirement for further training in this area, as they felt they lacked both the skills and knowledge required to deal with these exceptionally able pupils

Cell-Specific Inhibition of p38α as a Therapeutic Strategy for Inflammatory Bowel Disease

The abstract is included in the text

Chemokine decoy receptor D6 in inflammatory bowel disease (IBD) and IBD-associated colon cancer

The abstract is included in the text

Ectopic lymphoid tissue alters the chemokine gradient, increases lymphocyte retention and exacerbates murine ileitis

Background The earliest endoscopically-evident lesion in Crohn’s disease is the aphthous ulcer, which develops over ectopic lymphoid tissues (ie, inducible lymphoid follicles (ILF), tertiary lymphoid tissue (TLT)) in the chronically inflamed intestine. ILF/TLT are induced within effector sites by homeostatic lymphoid chemokines, but their role in the development of intestinal ILF/TLT and in the pathogenesis of Crohn’s disease is poorly understood. Design Using a mouse model of Crohn’s-like ileitis (TNFΔARE) which develops florid induction of ILF/TLT within its terminal ileum, the contribution of the CCR7/ CCL19/CCL21 chemokine axis during the development of TLT and its role in disease pathogenesis were assessed. Results Both CCL19 and CCL21 were increased within the inflamed ileum of TNFΔARE mice, which resulted in CCR7 internalisation and impaired T cell chemotaxis. ILF/ TLT were a major source of CCL19 and CCL21 and increased local synthesis, augmented recruitment/ retention of effector, naı¨ve and central memory T cell subsets within the inflamed ileum. Immunoblockade of CCR7 resulted in further effector T cell retention and exacerbation of ileitis. Conclusions Induction of ILF/TLT in the chronically inflamed intestine alters the homeostatic CCL19-CCL21 lymphoid-chemokine gradient and increases recruitment/ retention of effector CCR7+ T cell subsets within the terminal ileum, contributing to the perpetuation of chronic inflammation. Thus, blockade of CCR7 or its ligands might result in deleterious consequences for subjects with chronic inflammatory diseases

Flt3 ligand expands CD103+ dendritic cells and FoxP3+ T regulatory cells, and attenuates Crohn’s-like murine ileitis

Background Imprinting an effector or regulatory phenotype on naı¨ve T cells requires education at induction sites by dendritic cells (DC). Objectives To analyse the effect of inflammation on the frequency of mononuclear phagocytes (MP) and the effect of altering their frequency by administration of Flt3-L in chronic ileitis. Methods Using a tumour necrosis factor (TNF) driven model of ileitis (ie, TNFΔARE) that recapitulates many features of Crohn’s disease (CD), dynamic changes in the frequency and functional state of MP within the inflamed ileum were assessed by flow cytometry, immunofluorescence and real-time reverse-transcription PCR and by generating CX3CR1 GFP-reporter TNFΔARE mice. The effect of Flt3-L supplementation on the severity of ileitis, and the frequency of CD103+ DC and of FoxP3+ regulatory T cells was also studied in TNFΔARE mice. Results CD11cHi/MHCII+ MP accumulated in inflamed ilea, predominantly mediated by expansion of the CX3CR1+ MP subpopulation. This coincided with a decreased pro-regulatory CD103+ DC. The phenotype of these MP was that of activated cells, as they expressed increased CD80 and CD86 on their surface. Flt3-ligand administration resulted in a preferential expansion of CD103+ DC that attenuated the severity of ileitis in 20-week-old TNFΔARE mice, mediated by increased CD4+/CD25+/FoxP3+ regulatory T cells. Conclusions Results support a role for Flt3-L as a potential therapeutic agent in Crohn’s-like ileitis