Toll-Interacting Protein Regulates Immune Cell Infiltration and Promotes Colitis-Associated Cancer.

Expression of Toll-interacting protein (Tollip), a potent TLR modulator, decreases in patients with inflammatory bowel diseases (IBD), whereas Tollip <sup>-/-</sup> mice are susceptible to colitis. Tollip expression was shown to be reduced in sporadic adenoma . In contrast, we found variable Tollip expression in patients with colitis-associated adenomas. In Tollip <sup>-/-</sup> mice challenged to develop colitis-associated cancer (CAC), tumor formation was significantly reduced owing to decreased mucosal proliferative and apoptotic indexes. This protection was associated with blunt inflammatory responses without significant changes in microbial composition. mRNA expression of Cd62l and Ccr5 homing receptors was reduced in colons of untreated Tollip <sup>-/-</sup> mice, whereas CD62L <sup>+</sup> CD8 <sup>+</sup> T cells accumulated in the periphery. In Tollip-deficient adenomas Ctla-4 mRNA expression and tumor-infiltrating CD4 <sup>+</sup> Foxp3 <sup>+</sup> regulatory T cell (Treg) were decreased. Our data show that protection from CAC in Tollip-deficient mice is associated with defects in lymphocyte accumulation and composition in colitis-associated adenomas

Oral Probiotic Control Skin Inflammation by Acting on Both Effector and Regulatory T Cells

Probiotics are believed to alleviate allergic and inflammatory skin disorders, but their impact on pathogenic effector T cells remains poorly documented. Here we show that oral treatment with the probiotic bacteria L. casei (DN-114 001) alone alleviates antigen-specific skin inflammation mediated by either protein-specific CD4+ T cells or hapten-specific CD8+ T cells. In the model of CD8+ T cell-mediated skin inflammation, which reproduces allergic contact dermatitis in human, inhibition of skin inflammation by L. casei is not due to impaired priming of hapten-specific IFNγ-producing cytolytic CD8+ effector T cells. Alternatively, L. casei treatment reduces the recruitment of CD8+ effector T cells into the skin during the elicitation (i.e. symptomatic) phase of CHS. Inhibition of skin inflammation by L. casei requires MHC class II-restricted CD4+ T cells but not CD1d-restricted NK-T cells. L casei treatment enhanced the frequency of FoxP3+ Treg in the skin and increased the production of IL-10 by CD4+CD25+ regulatory T cells in skin draining lymph nodes of hapten-sensitized mice. These data demonstrate that orally administered L. casei (DN-114 001) efficiently alleviate T cell-mediated skin inflammation without causing immune suppression, via mechanisms that include control of CD8+ effector T cells and involve regulatory CD4+ T cells. L. casei (DN-114 001) may thus represent a probiotic of potential interest for immunomodulation of T cell-mediated allergic skin diseases in human

The Role of Intestinal Microbiota in the Development and Severity of Chemotherapy-Induced Mucositis

Mucositis, also referred to as mucosal barrier injury, is one of the most debilitating side effects of radiotherapy and chemotherapy treatment. Clinically, mucositis is associated with pain, bacteremia, and malnutrition. Furthermore, mucositis is a frequent reason to postpone chemotherapy treatment, ultimately leading towards a higher mortality in cancer patients. According to the model introduced by Sonis, both inflammation and apoptosis of the mucosal barrier result in its discontinuity, thereby promoting bacterial translocation. According to this five-phase model, the intestinal microbiota plays no role in the pathophysiology of mucositis. However, research has implicated a prominent role for the commensal intestinal microbiota in the development of several inflammatory diseases like inflammatory bowel disease, pouchitis, and radiotherapy-induced diarrhea. Furthermore, chemotherapeutics have a detrimental effect on the intestinal microbial composition (strongly decreasing the numbers of anaerobic bacteria), coinciding in time with the development of chemotherapy-induced mucositis. We hypothesize that the commensal intestinal microbiota might play a pivotal role in chemotherapy-induced mucositis. In this review, we propose and discuss five pathways in the development of mucositis that are potentially influenced by the commensal intestinal microbiota: 1) the inflammatory process and oxidative stress, 2) intestinal permeability, 3) the composition of the mucus layer, 4) the resistance to harmful stimuli and epithelial repair mechanisms, and 5) the activation and release of immune effector molecules. Via these pathways, the commensal intestinal microbiota might influence all phases in the Sonis model of the pathogenesis of mucositis. Further research is needed to show the clinical relevance of restoring dysbiosis, thereby possibly decreasing the degree of intestinal mucositis

Spécificité des stratégies de coping des patients en rémission de la maladie de Crohn : une étude qualitative

International audienceIntroduction: Crohn's disease (CD), a chronic inflammatory bowel disease, has strong psychological and social repercussions related to the specificity of the symptomatology. To better understand how patients cope with the disease, coping strategies have been studied but without taking into account the specificity of the CD experience.Objective: Our objective is to identify the perceived coping strategies used by patients in relation to their illness experience.Method: Using a qualitative approach, semi-structured interviews and thematic content analysis with 33 CD patients in remission were conducted.Results: Our results highlight that some of the coping strategies used are not taken into account by the coping scales frequently used in the literature. Indeed, the illness experience appears to be fundamental in the establishment of new strategies based on the experiential knowledge patients use to reduce the stress induced by a potential relapse. Moreover, coping strategies based on positive emotions are also implemented, and they enable patients to make sense of the disease.Conclusion: The coping strategies, i.e., “experiential knowledge” and “positive emotions”, may shed more light on the complexity of the illness experience of CD patients and allow us to make recommendations concerning the psychological support of patients.Introduction: La maladie de Crohn (MC), maladie inflammatoire chronique de l’intestin, entraîne de fortes répercussions psychologiques et sociales en lien avec la spécificité de la symptomatologie. Pour mieux comprendre comment les patients font face à la maladie, les stratégies de coping ont été étudiées mais sans prendre en compte la spécificité du vécu de la MC.Objectif: Identifier les stratégies de coping perçues utilisées par les patients en rapport au vécu de leur maladie.Méthode: Trente-trois entretiens semi-directifs ont été menés auprès de patients MC en rémission et analysés via une analyse de contenu thématique.Résultats: Nos résultats mettent en évidence des stratégies de coping absentes des échelles de coping : l’expérience de la maladie paraît fondamentale dans l’établissement de nouvelles stratégies centrées sur des savoirs expérientiels utilisés afin de réduire le stress induit par la survenue potentielle d’une rechute. Des stratégies de coping basées sur des émotions positives à partir desquelles des stratégies de mises en sens de la maladie peuvent également être mises en place.Conclusion: Les stratégies de coping « savoir expérientiel » et « émotions positives » peuvent permettre de mieux comprendre la complexité du vécu de la MC et orienter l’accompagnement psychologique des patients

Letter: mucosal healing in ulcerative colitis - higher relevance than in Crohn's disease? Authors' reply

International audienc

My Career Chapter: Guidance Counsellors' Appraisal of its Suitability for Adolescents

This paper presents an investigation into the properties of a new narrative technique for career assessment and counselling, My Career Chapter: A Dialogical Autobiography. This technique is used to facilitate clients' construction of a meaningful career-related autobiography. Previous research indicates the usefulness of My Career Chapter for adult clients and its alignment with recommendations for the development and application of qualitative assessment and counselling techniques. This study specifically commences research into the technique's applicability for adolescents. A focus group, comprised of guidance counselling professionals whose work primarily pertained to the needs of adolescents, found that there is potential to develop a version of My Career Chapter that is suitable for adolescents

Infliximab induces clinical resolution of sacroiliitis that coincides with increased circulating FOXP3(+) T cells in a patient with IPEX syndrome

International audienceImmune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare monogenic primary immunodeficiency due to mutations of FOXP3, a master transcription factor of regulatory T cells (Treg). IPEX syndrome leads to fatal course in most cases during early childhood or severe multi-organ immune-mediated disorders in patients who survive. Currently hematopoietic stem cell transplantation represents the only known effective cure for IPEX syndrome. However, older patients with a mild disease not severe enough to justify transplantation, raise concerns regarding the appropriate therapeutic management, which is therefore based on supportive and replacement therapies combined with pharmacological immunosuppression. Herein, we report the case of a 22-year-old man with an incomplete IPEX syndrome without endocrine disorders having suffered from severe enteropathy since his birth treated with a combination of various immunosuppressant agents. He developed severe exacerbation of inflammatory low back pain in relation to sacroiliitis. Eventually, infliximab was initiated to control his back pain with rapid resolution as well as digestive improvement and also reduced biological inflammatory markers. In parallel, flow cytometry analysis revealed an increase in the frequency of circulating FOXP3+ CD4+ Treg cells. Altogether these data highlight that anti-TNF may represent a promising therapeutic option in patients with IPEX syndrome

Accuracies of fecal calprotectin, lactoferrin, M2-pyruvate kinase, neopterin and zonulin to predict the response to infliximab in ulcerative colitis

International audienceBACKGROUND: Fecal markers might predict the response to anti-TNFalpha in ulcerative colitis (UC). AIMS: To compare the performance of fecal calprotectin (fCal), lactoferrin (fLact), M2-PK (fM2-PK), neopterin (fNeo), and zonulin (fZon) to predict the response to therapy in active UC patients. METHODS: Disease activity from 31 consecutive patients with an active UC, treated with infliximab (IFX) was assessed by the Mayo score at baseline and at week 14 and by the partial Mayo score at W52 and stool samples collected for fecal marker measurements at W0, W2, and W14. RESULTS: At W14, 19 patients (61%) were responders to IFX induction. The median levels of fCal, fLact and fM2-PK drop dramatically from baseline to W14 in clinical responders. At W2, fM2-PK, fLact and fCal levels predicted accurately the response to IFX induction. At W14, fLact, fCal, and fM2-PK were individually reliable markers to predict sustained response at W52. The performances of fNeo and fZon were weaker in this setting. CONCLUSIONS: The performance of fM2-PK at W2 to predict response to induction therapy with IFX was superior to that of fLact and fCal, whereas monitoring fLact was the best tool to predict adequately the course of the disease at one year under maintenance IFX in UC