Hapten-induced colitis associated with maintained Th1 and inflammatory responses in IFN-γ receptor-deficient mice

Camoglio, L.; Velde, Anje A. te; Boer, Angela G. E. M. de; Kate, Fibo J. ten; Köpf, Manfred; Deventer, Sander J. van

doi:10.1002/(sici)1521-4141(200005)30:5<1486::aid-immu1486>3.0.co;2-8

Cited by 81 publications

(47 citation statements)

References 29 publications

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“…7 Macroscopic signs of inflammation characteristic for TNBS-induced colitis comprise marked oedema and mucosal thickening, which are accompanied by increased colon weight. 18 Results of our study are in agreement with these observations. The presence of an accentuated oedema in the colon was determined, with marked inflammatory changes that were most conspicuous the second day following TNBS-ethanol administration.…”

Section: Resultssupporting

confidence: 91%

Relevance of DPP IV/CD26 among the Gut-brain Axis during Experimental Colitis

Pučar¹,

Detel²,

Buljević³

et al. 2012

Croat. Chem. Acta

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Abstract. Inflammatory bowel diseases (IBD) represent a group of chronic conditions of the gastrointestinal tract of unknown etiology. Latest knowledge accentuates the bidirectional connection between the central and enteric nervous systems. An important role of peptidases has been proposed in maintaining the homeostasis in the gut. One of them is dipeptidil-peptidase IV (DPP IV/CD26), a multifunctional glycoprotein found in both soluble and membrane-bound form in living organisms. In order to evaluate the relevance of DPP IV/CD26 among the gut-brain axis, a TNBS (Crohn-like) model of colitis has been induced in CD26 deficient and wild type mice. Results of this study showed that CD26 deficient mice show specificity in histological damage compared to wild type mice. A decreased DPP IV/CD26 activity was found in serum, colon and brain in wild type mice with colitis, while CD26 protein expression was increased in colon of those mice. DPP IV/CD26-like activity was decreased only in colon of CD26 deficient mice. Changes occurring during inflammatory processes in colon reflected on investigated parameters in brain. Therefore, our results indicate the importance of the gut-brain axis in the pathogenesis of IBD.

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Section: Resultssupporting

confidence: 91%

Relevance of DPP IV/CD26 among the Gut-brain Axis during Experimental Colitis

Pučar¹,

Detel²,

Buljević³

et al. 2012

Croat. Chem. Acta

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“…In assessing prototypic Th1 responses, we were surprised by the lack of an increased IFN-␥ mRNA response 3 days after DNBS treatment, yet others have shown that elevated IFN-␥ mRNA occurs only 1-2 wk after DNBS treatment (33). Indeed IFN-␥ signaling is dispensable in this model of colitis (30,31). However, it should also be noted that helminth infection has been associated with reduced IFN-␥ mRNA and splenocyte IFN-␥ production 7 days after TNBS treatment (10,12).…”

Section: Discussionmentioning

confidence: 88%

Neutralizing Anti-IL-10 Antibody Blocks the Protective Effect of Tapeworm Infection in a Murine Model of Chemically Induced Colitis

Hunter

Wang

Hirota

et al. 2005

The Journal of Immunology

151

212

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There is increasing evidence that parasitic helminth infection has the ability to ameliorate other disease conditions. In this study the ability of the rat tapeworm, Hymenolepis diminuta, to modulate dinitrobenzene sulfonic acid (DNBS)-induced colitis in mice is assessed. Mice receiving DNBS (3 mg intrarectally) developed colitis by 72 h after treatment. Mice infected 8 days before DNBS with five H. diminuta larvae were significantly protected from the colitis, as gauged by reduced clinical disease, histological damage scores, and myeloperoxidase levels. This anticolitic effect was dependent on a viable infection and helminth rejection, because no benefit was observed in mice given killed larvae or in infected STAT6 knockout mice or rats, neither of which eliminate H. diminuta. The anticolitic effect of H. diminuta was associated with increased colonic IL-10 mRNA and stimulated splenocytes from H. diminuta- plus DNBS-treated mice produced more IL-10 than splenocytes from DNBS-only treated mice. Coadministration of an anti-IL-10 Ab blocked the anticolitic effect of prophylactic H. diminuta infection. Also, mice infected 48 h after DNBS treatment showed an enhanced recovery response. Finally, using a model of OVA hypersensitivity, we found no evidence of concomitant H. diminuta infection enhancing enteric responsiveness to subsequent ex vivo OVA challenge. The data show that a viable infection of H. diminuta in a nonpermissive system exerts a profound anticolitic effect (both prophylactically and as a treatment) that is mediated at least in part via IL-10 and does not predispose to enhanced sensitivity to bystander proteins.

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“…Th2 cells have been shown to mediate allergic responses, whilst Th1 cells are generally associated with autoimmune diseases. However, the concept of Th1-mediated autoimmunity has been challenged by the finding that mice lacking IFN-c, the prototypic Th1 cytokine, are highly susceptible to inflammatory and autoimmune diseases including colitis [26], encephalitis (EAE) [27] and myocarditis (EAM) [8,9]. We now know that EAE is mediated by IL-17 produced by a recently discovered population of CD4 cells termed Th17 [28,29], which require IL-23 for their development [12][13][14].…”

Section: Discussionmentioning

confidence: 99%

Neutralization of IL‐17 by active vaccination inhibits IL‐23‐dependent autoimmune myocarditis

et al. 2006

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The most common reason for heart failure in young adults is dilated cardiomyopathy often resulting from myocarditis. Clinical studies and animal models provide evidence that an autoimmune response against heart myosin is the underlying reason for the disease. IL-12 has been suggested to play a key role in development of experimental autoimmune myocarditis (EAM), as IL-12p40 and IL-12Rb1 knockouts are protected from disease. In this study, we have compared IL-12p40 -/-mice, IL-12p35 -/-mice and mice treated with a neutralizing IL-23 antibody in EAM and found that in fact IL-23, not IL-12, is responsible for inflammatory heart disease. However, these cytokines appear to have redundant activity for priming and expansion of autoreactive CD4 T cells, as specific T cell proliferation was only defective in the absence of both cytokines. IL-23 has been suggested to promote a pathogenic IL-17-producing T cell population. We targeted IL-17 by capitalizing on an active vaccination approach that effectively breaks B cell tolerance. Neutralization of IL-17 reduced myocarditis and heart autoantibody responses, suggesting that IL-17 is the critical effector cytokine responsible for EAM. Thus, targeting of IL-23 and IL-17 by passive and active vaccination strategies holds promise as a therapeutic approach to treat patients at risk for development of dilated cardiomyopathy. IntroductionDilated cardiomyopathy has been associated with infection by certain viruses (specific strains of coxsackie virus and cytomegalovirus), bacteria (Streptococci, Borrelia, Cornybacterium diphtheriae) or protozoa (Trypansosoma cruzi) [1]. Infection causes an acute heart muscle inflammation (myocarditis) followed in susceptible individuals by an autoimmune response primarily directed against heart muscle myosin, leading to myocardial dilation and heart failure.In experimental animal models, myocarditis can be induced in the absence of infection by immunization of susceptible mice (and rats) with cardiac myosin [2] or a pathogenic peptide located in the head portion of [4,6,7]. Based on studies in mice deficient for IL-12p40 or IL-12Rb1, we and others have suggested that IL-12 is critical for disease development [8,9]. However, more recently it became clear that the heterodimers IL-12 (p40/35) and IL-23 (p40/p19) share the p40 subunit and the b1 chain of their receptor and that IL-23, rather than IL-12, is essential for inflammatory responses in the central nervous system and joints [10,11]. IL-23 has been implicated in the development of a recently described subset of CD4 T cells characterized by the production of IL-17, . Notably, these cells have been shown to exert a pathogenic role in several autoimmune and inflammatory diseases including EAE, collagen-induced arthritis and T cell-mediated colitis [15][16][17]. Development of this subset is promoted by IL-23, TGF-b and IL-6 and inhibited by [18][19][20][21][22]. We report here that IL-23 and IL-17 are pathogenic mediators of cardiac inflammation, which could be successfully targeted by immunothe...

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Hapten-induced colitis associated with maintained Th1 and inflammatory responses in IFN-γ receptor-deficient mice

Cited by 81 publications

References 29 publications

Relevance of DPP IV/CD26 among the Gut-brain Axis during Experimental Colitis

Relevance of DPP IV/CD26 among the Gut-brain Axis during Experimental Colitis

Neutralizing Anti-IL-10 Antibody Blocks the Protective Effect of Tapeworm Infection in a Murine Model of Chemically Induced Colitis

Neutralization of IL‐17 by active vaccination inhibits IL‐23‐dependent autoimmune myocarditis

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