Eosinophils and IL-33 Perpetuate Chronic Inflammation and Fibrosis in a Pediatric Population with Stricturing Crohn's Ileitis.
Inflammatory Bowel Diseases 21(10):2429 (2015)
Fibrostenosis and stricture are well-recognized endpoints in Crohn's disease (CD). We hypothesized that stricturing CD is characterized by eosinophilia and epithelial IL-33. We proposed that eosinophil exposure to IL-33 would perpetuate inflammatory chronicity and subsequent fibrostenosis.
Loss of n-6 fatty acid induced pediatric obesity protects against acute murine colitis.
FASEB Journal 29(8):3151 (2015)
Dietary influences may affect microbiome composition and host immune responses, thereby modulating propensity toward inflammatory bowel diseases (IBDs): Crohn disease (CD) and ulcerative colitis (UC). Dietary n-6 fatty acids have been associated with UC in prospective studies. However, the criti...
Regulatory T cells suppress CD4+ T cells through NFAT-dependent transcriptional mechanisms.
EMBO Reports 15(9):991 (2014)
Regulatory T cells (Tregs) control autoreactive T cells by inhibiting activation-induced proliferation and cytokine expression. The molecular mechanisms responsible for the inactivation of effector T cells by Tregs remain yet to be fully characterized. We report that T-helper cells stimulated in...
Targeted inhibition of heat shock protein 90 suppresses tumor necrosis factor-α and ameliorates murine intestinal inflammation.
Inflammatory Bowel Diseases 20(4):685 (2014)
Inflammatory bowel diseases are chronic intestinal inflammatory diseases thought to reflect a dysregulated immune response. Although antibody-based inhibition of tumor necrosis factor-α (TNF-α) has provided relief to many inflammatory bowel diseases patients, these therapies are either ineffecti...
Antitumor necrosis factor, infliximab, and adalimumab: use with caution in eosinophilic bowel disease.
Journal of Pediatric Gastroenterology and Nutri... 57(4):e25 (2013)
Diagnosis and treatment of perianal Crohn disease: NASPGHAN clinical report and consensus statement.
Journal of Pediatric Gastroenterology and Nutri... 57(3):401 (2013)
Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract that includes both Crohn disease (CD) and ulcerative colitis. Abdominal pain, rectal bleeding, diarrhea, and weight loss characterize both CD and ulcerative colitis. The incidence of IBD in the United Sta...
Alpha-1-antitrypsin therapy ameliorates acute colitis and chronic murine ileitis.
Inflammatory Bowel Diseases 19(9):1964 (2013)
Fecal alpha-1-antitrypsin (AAT) clearance has been a marker of clinical disease severity in inflammatory bowel diseases (IBDs) for many years. Although AAT deficiency is more often associated with lung and liver pathologies, AAT-deficient patients with concomitant IBD have been shown to develop ...
Challenges in IBD research: update on progress and prioritization of the CCFA's research agenda.
Inflammatory Bowel Diseases 19(4):677 (2013)
Hypoxia-inducible factor-1 alpha-dependent induction of FoxP3 drives regulatory T-cell abundance and function during inflammatory hypoxia of the mucosa.
PNAS 109(41):E2784 (2012)
Recent studies have demonstrated dramatic shifts in metabolic supply-and-demand ratios during inflammation, a process resulting in localized tissue hypoxia within inflammatory lesions ("inflammatory hypoxia"). As part of the adaptive immune response, T cells are recruited to sites of inflammator...
Histone deacetylase 6 and heat shock protein 90 control the functions of Foxp3(+) T-regulatory cells.
Molecular and Cellular Biology 31(10):2066 (2011)
Foxp3(+) T-regulatory cells (Tregs) are key to immune homeostasis such that their diminished numbers or function can cause autoimmunity and allograft rejection. Foxp3(+) Tregs express multiple histone/protein deacetylases (HDACs) that regulate chromatin remodeling, gene expression, and protein f...
A novel method to enhance informed consent: a prospective and randomised trial of form-based versus electronic assisted informed consent in paediatric endoscopy.
Journal of Medical Ethics 37(4):194 (2011)
To evaluate the adequacy of paediatric informed consent and its augmentation by a supplemental computer-based module in paediatric endoscopy.
The Consent-20 instrument was developed and piloted on 47 subjects. Subsequently, parents of 101 children undergoing first-time, diagnostic upper endoscop...
Inhibition of HDAC9 increases T regulatory cell function and prevents colitis in mice.
Gastroenterology 138(2):583 (2010)
Foxp3+ T regulatory cells (Tregs) help prevent autoimmunity, and increases in their numbers of functions could decrease the development of inflammatory bowel disease. Like other cells, Foxp3+ Tregs express histone/protein deacetylases (HDACs), which regulate chromatin remodeling and gene express...
Immunomodulatory effects of deacetylase inhibitors: therapeutic targeting of FOXP3+ regulatory T cells.
Nature Reviews: Drug Discovery 8(12):969 (2009)
Classical zinc-dependent histone deacetylases (HDACs) catalyse the removal of acetyl groups from histone tails and also from many non-histone proteins, including the transcription factor FOXP3, a key regulator of the development and function of regulatory T cells. Many HDAC inhibitors are in can...
Foxp3 processing by proprotein convertases and control of regulatory T cell function.
Journal of Biological Chemistry 284(9):5709 (2009)
Foxp3 is a 47-kDa transcription factor central to regulatory T cell (Treg) function. The importance of Foxp3(+) Tregs in controlling self-reactive T cells and preventing autoimmunity is well established. Our analysis of Foxp3 expression in natural Tregs led to identification of a shorter 41-kDa ...
Strategies to cure experimental autoimmune colitis using antigen-specific Foxp3+ regulatory T cells.
Gastroenterology 134(7):2171 (2008)
A 9-month-old girl with chronic diarrhea.
Medscape journal of medicine 10(8):195 (2008)
Deacetylase inhibition promotes the generation and function of regulatory T cells.
Nature Medicine 13(11):1299 (2007)
Histone/protein deacetylases (HDACs) regulate chromatin remodeling and gene expression as well as the functions of more than 50 transcription factors and nonhistone proteins. We found that administration of an HDAC inhibitor (HDACi) in vivo increased Foxp3 gene expression, as well as the product...
Histone deacetylase inhibitors and transplantation.
Current Opinion in Immunology 19(5):589 (2007)
Simply detecting the presence or absence of Foxp3, a transcription factor characteristic of naturally occurring CD4+ CD25+ regulatory T cells (Tregs), now appears of minimal value in predicting the outcome of immunologic responses, since dividing human CD4+ effector T cells can induce Foxp3 with...