Basophils are a rare population of granulocytes that have long been associated with IgE-mediated and Th2-associated allergic diseases. However, the role of basophils in Th17 and/or Th1 diseases has not been reported. In the present study, we report that basophils can be detected in the mucosa of Th17-associated lung and inflammatory bowel disease and accumulate in inflamed colons containing large quantities of IL-33. We also demonstrate that circulating basophils increased memory Th17 responses. Accordingly, IL-3-or IL-33-activated basophils amplified IL-17 release in effector memory T cells (T EM ), central memory T cells (T CM) IntroductionBasophils are the least abundant of the granulocyte population, accounting for only 0.5%-1% of circulating leukocytes, and, together with eosinophils and mast cells (MCs), have long been associated with allergic diseases and helminth infections. [1][2][3][4] Like MCs, basophils express the tetrameric form of the high-affinity receptor for IgE (Fc⑀RI) and are a major source of histamine, which is stored in their cytoplasmic basophilic granules. Basophils and MCs belong to distinct cell lineages and are biologically very different. 5 Basophils are short-lived circulating cells (estimated half-life of 2 days) that differentiate and mature in the BM, whereas MCs are long-lived, tissue-resident cells that differentiate in peripheral tissues from locally recruited circulating CD34 ϩ precursors released from the BM. MCs are easily detectable at the interface of the organism with the external world; in contrast, basophils are rarely found in normal tissues, but can be detected by immunohistochemistry in inflamed tissues of patients with asthma, allergic rhinitis, and various allergic skin diseases. 1,6,7 However, the presence of basophils in the mucosa of patients with inflammatory diseases that are independent of IgE has not been reported.The CD4 T cells play a key role in orchestrating the pathologic immune reaction of chronic inflammatory disorders. It is now known that Th17 effectors play a crucial role in pulmonary cystic fibrosis (CF). 8 Similarly, Th17 and Th1 cells are involved in mucosa-associated chronic disorders such as inflammatory bowel disease (IBD), which include Crohn's disease (CD) and ulcerative colitis (UC). 9-11 Specifically, CD is a chronic and relapsing T cell-driven inflammatory disease of the entire gastrointestinal tract. CD4 effector T cells are generated in draining lymph nodes and recruited into the intestinal tissues, where they contribute to the inflammatory process and tissue destruction. 9 Once initiated, inflammation is first characterized by the expression of proinflammatory cytokines involved in innate immunity (ie, IL-12, TNF-␣, and IL-23), followed by those involved in adaptive immunity (ie, . 9,12 APC-derived IL-1, together with IL-6, promotes the development of human Th17 cells in vitro. 13 IL-23 promotes the expansion of memory Th17 cells. 14 In mice, IL-23 drives pathogenic Th17/Th1 cells. 15 Double IL-17-and IFN-␥-producing CD4 T cells ar...
CD172a+ cells producing IL-1β and TNF are increased in inflamed tissues in Crohn’s disease and can be targeted by CD47 fusion protein.
<p>ABSTRACT</p><p><strong>Background</strong>: Proton pump inhibitors (PPIs) are widely prescribed for gastrointestinal conditions, such as gastroesophageal reflux disease and dyspepsia, and for prevention of gastric ulcer. Although previous reports<br />have described inappropriate prescription of PPIs in the hospital setting, data from the community are lacking.</p><p><strong>Objective</strong>: To assess PPI prescriptions in the ambulatory setting.</p><p><strong>Methods</strong>: Patients presenting to the emergency department of a teaching hospital between June 2016 and March 2017 were prospectively assessed for use of a PPI at home. The appropriateness of PPI prescription was<br />evaluated on the basis of an interview with the patient and review of the medical record. The indication for PPI therapy was verified against current guidelines for the province of Quebec.</p><p><strong>Results</strong>: Over the 9-month study period, 2417 patients were screened, of whom 871 were included in the study. In relation to the Quebec guidelines, PPI prescription was inappropriate for 267 (30.7%) of the patients. When prescription of PPI for ulcer prevention in certain groups of patients (age ≥ 65 years and using acetylsalicylic acid or platelet aggregation inhibitors; age ≥ 75 years and using celecoxib) was re-classified as appropriate, the proportion of inappropriate PPI prescriptions declined to 20.3% (177/871).</p><p><strong>Conclusions</strong>: These findings suggest that inappropriate prescribing of PPIs remains problematic in the community setting in the province of Quebec.</p><p>RÉSUMÉ</p><p><strong>Contexte</strong> : Les inhibiteurs de la pompe à protons (IPP) sont largement prescrits pour traiter les troubles gastro-intestinaux, comme le reflux gastro-oesophagien et la dyspepsie, et pour prévenir l’ulcère gastrique. Bien<br />que des rapports antérieurs aient parlé de la prescription inadéquate des IPP dans les établissements de santé, il n’y a pas de données provenant de la communauté.</p><p><strong>Objectif</strong> : Évaluer la pertinence des prescriptions d’IPP dans un milieu ambulatoire.</p><p><strong>Méthodes</strong> : Les patients se présentant au service des urgences d’un hôpital universitaire entre juin 2016 et mars 2017 ont été évalués de façon prospective relativement à l’utilisation d’un IPP à la maison. La pertinence de la prescription d’un IPP a été jugée d’après une entrevue avec le patient et l’analyse du dossier médical. On a vérifié si l’indication pour un traitement par IPP respectait les lignes directrices actuelles du Québec.</p><p><strong>Résultats</strong> : Sur une période de neuf mois, 2 417 patients ont été évalués et 871 d’entre eux ont été admis à l’étude. Par rapport aux lignes directrices du Québec, la prescription d’IPP était inadéquate pour 267 (30,7 %) des patients. Or, si la prescription d’IPP pour prévenir l’ ulcère gastrique chez certains groupes de patients (âgés de 65 ans ou plus et prenant de l’acide acétylsalicylique ou un antiagrégant plaquettaire; âgés de 75 ans ou plus et prenant du célécoxib) était reclassée comme adéquate, la proportion de prescriptions d’IPP inadéquates reculait à 20,3 % (177/871).</p><p><strong>Conclusions</strong> : Ces résultats laissent croire que les prescriptions inadéquates d’IPP demeurent un problème dans le contexte communautaire au Québec.<br /><br /></p>
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