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| 1 | Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy显示文摘AIM To study the innate immune function in ulcerative colitis(UC) patients who fail to respond to anti-tumor necrosis factor(TNF) therapy.METHODS Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell(PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor(TLR) expression and cytokine production post TLR stimulation was assessed in UC 'responders'(n = 12) and 'non-responders'(n = 12) and compared to healthy controls(n = 12). Erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) levels were measured in blood to assess disease severity/activity and inflammation. Pro-inflammatory(TNF, IL-1β, IL-6), immuno-regulatory(IL-10), Th1(IL-12, IFNγ) and Th2(IL-9, IL-13, IL-17A) cytokine expression was measured with enzyme-linked immunosorbent assay while TLR cellular composition and intracellular signalling was assessed with FACS.RESULTS Prior to anti-TNF therapy, responders and nonresponders had similar level of disease severity and activity. PBMC's ability to respond to TLR stimulation was not affected by TNF therapy, patient's severity of the disease and inflammation or their medication use. At baseline, non-responders had elevated innate but not adaptive immune responses compared to responders(P < 0.05). Following TLR stimulation, nonresponders had consistently reduced innate cytokine responses to all TLRs compared to healthy controls(P < 0.01) and diminished TNF(P < 0.001) and IL-1β(P < 0.01) production compared to responders. This innate immune dysfunction was associated with reduced number of circulating plasmacytoid dendritic cells(p DCs)(P < 0.01) but increased number of CD4+ regulatory T cells(Tregs)(P = 0.03) as well as intracellular accumulation of IRAK4 in non-responders following TLR-2,-4 and-7 activation(P < 0.001). CONCLUSION Reduced innate immunity in non-responders may explain reduced efficacy to anti-TNF therapy. These serological markers may prove useful in predicting the outcome of costly anti-TNF therapy. | Angela C Baird Dominic Mallon Graham Radford-Smith Julien Boyer Thierry Piche Susan L Prescott Ian C Lawrance Meri K Tulic | 2016 | World Journal of Gastroenterology2016，22，41： | 10 |
| 2 | Modification of the inflammatory response to allergen challenge after exposure to bacterial lipopolysaccharide显示文摘 | Tulic MK Wale JL Holt PG | 2000 | Am J Respir Cell Mol Biol2000，22，： | 1 |
| 3 | Immunobiology of Asthma 显示文摘 | Hamid Q Tulic M | 2009 | AnnuRev Physiol2009，71，14： | 1 |
| 4 | Tools used to measure airway remodelling in research显示文摘 | Bergeron C Tulic MK Hamid Q | 2007 | Eur Respir J2007，29，10： | 1 |
| 5 | Oral corticosteroids decrease eosinophil and CC chemokine expression but increase neutrophil, IL-8, and IFN-gamma-ind,ucible protein 10 expression in asthmatic airway mucosa显示文摘 | Fukakusa M Bergeron C Tulic MK | 2005 | Allergy Clin Immunol2005，115，2： | 1 |
| 6 | Microbial superantigens induce glucocorticoid receptor beta and steroid resistance in a nasal explant model显示文摘 | Fakhri S Tulic M Christodoulopoulos P | 2004 | Laryngoscope2004，114，： | 1 |
| 7 | Amb a 1-immuno-stimu-latory oligodeoxynucleotide conjugate immunotherapy decreases the nasal inflammatory response显示文摘 | Tulic MK Fiset PO Christodoulopoulos P | 2004 | J Allergy Clin Immunol2004，113，2： | 1 |
| 8 | A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9 expression and mucus production in bronchial epithelium of patients with asthma显示文摘 | Toda M Tulic MK Levitt RC | 2002 | J Allergy Clin Immunol2002，109，2： | 1 |
| 9 | Vitamin D deficiency as a strong predictor of asthma in children显示文摘 | Bener A Ehlayel MS Tulic MK | 2012 | Int Arch Allergy Immunol2012，157，2： | 1 |
| 10 | Role of Toll-like receptor 4 in protection by bacterial lipopolyseceharide in the nasal mucosa of atopie children but not adults显示文摘 | Tulic MK Fiset PO Manoukian JJ | 2004 | Lancet2004，363，9422： | 1 |
| 11 | Small airway inflammation in asthma显示文摘 | Tulic MK Christodoulopoulos P Hamid Q | | 0，，： | 1 |
| 12 | Role of Toll-like receptor 4 in protection by bacterial lipopolysac- charide in the nasalmucosa of atopic children but not adults显示文摘 | Tulic M K Fiset P O Manoukian J J | 2004 | Lancet2004，363，： | 1 |
| 13 | Microbial superantigens induce glucocorticoid receptor beta and steroid resistance in a nasal explant model显示文摘 | FAKHRI S TULIC M CHRISTODOULOPOULOS P | 2004 | Laryngoscope2004，114，： | 1 |
| 14 | Roll of toll-like receptor 4 in protection by bacterial lipopolysaccharide in the nasal mucosa of atopic children but not adults 显示文摘 | Tulic MK Fiset PO Manoukian J J | 2004 | Lancet2004，363，： | 1 |
| 15 | Urinary prostate-specific antigen:predictor of benign prostatic hyperplasia progres-sion? 显示文摘 | PEJCIC T P TULIC CDZ LALIC N V | 2013 | Can J Urol2013，20，2： | 1 |
| 16 | Dedifferentiated chondrosarcoma:our clinico-pathological experience and dilemmas in 25 cases显示文摘 | Sopta J Dordevic A Tulic G | 2008 | J Cancer Res Clin Oncol2008，134，2： | 1 |
| 17 | Airway remodelling in asthma: frombenchside to clinical practice显示文摘 | Bergeron C Tulic M K Hamid Q | 2010 | Can Respir J2010，17，4： | 1 |
| 18 | Small airway inflammation in asthma显示文摘 | Tulic MK Christodoulopoulos P Hamid Q | 2001 | Respir Res2001，2，6： | 1 |
| 19 | TLR4 polymorphisms mediate impaired responses to respiratory syncytial virus and lipopo- lysaccharide 显示文摘 | Tulic MK Hurrelbrink RJ Prgle CM | 2007 | J Immunol2007，179，1： | 1 |
| 20 | Arab a 1-immunostim- ulatory oligodeoxynucleotide conjugate immunotherepy decreases the nasal inflammatory response显示文摘 | Tulic MK Fiset PO Christodoulopoulos P | 2004 | J Allergy Clin lmmunol2004，113，2： | 1 |
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