Immunology of the gut and liver: a love/hate relationship

Adams, David H.; Eksteen, Bertus; Curbishley, Stuart M.

doi:10.1136/gut.2007.122168

Cited by 63 publications

(55 citation statements)

References 160 publications

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“…It is now more apparent that the nature of the microbiota can be a major exacerbating or ameliorating factor in the rate and extent of progression in rodent autoimmune disease (3,58). In humans, such interplay has been suggested in intestinal, kidney (7), liver (59), and joint disease (60), and, indeed, there is mucosal firewall breach in celiac disease, which has many nonmucosal autoimmune sequelae (8,61). These parallels between BAFF-Tg mice and human IgAN may provide a new framework to explore connections between mucosal environments and the renal pathology.…”

Section: Figurementioning

confidence: 99%

Mice overexpressing BAFF develop a commensal flora–dependent, IgA-associated nephropathy

McCarthy¹,

Kujawa²,

Wilson³

et al. 2011

J. Clin. Invest.

236

165

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B cell activation factor of the TNF family (BAFF) is a potent B cell survival factor. BAFF overexpressing transgenic mice (BAFF-Tg mice) exhibit features of autoimmune disease, including B cell hyperplasia and hypergammaglobulinemia, and develop fatal nephritis with age. However, basal serum IgA levels are also elevated, suggesting that the pathology in these mice may be more complex than initially appreciated. Consistent with this, we demonstrate here that BAFF-Tg mice have mesangial deposits of IgA along with high circulating levels of polymeric IgA that is aberrantly glycosylated. Renal disease in BAFF-Tg mice was associated with IgA, because serum IgA was highly elevated in nephritic mice and BAFF-Tg mice with genetic deletion of IgA exhibited less renal pathology. The presence of commensal flora was essential for the elevated serum IgA phenotype, and, unexpectedly, commensal bacteria-reactive IgA antibodies were found in the blood. These data illustrate how excess B cell survival signaling perturbs the normal balance with the microbiota, leading to a breach in the normal mucosal-peripheral compartmentalization. Such breaches may predispose the nonmucosal system to certain immune diseases. Indeed, we found that a subset of patients with IgA nephropathy had elevated serum levels of a proliferation inducing ligand (APRIL), a cytokine related to BAFF. These parallels between BAFF-Tg mice and human IgA nephropathy may provide a new framework to explore connections between mucosal environments and renal pathology.

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Section: Figurementioning

confidence: 99%

Mice overexpressing BAFF develop a commensal flora–dependent, IgA-associated nephropathy

McCarthy¹,

Kujawa²,

Wilson³

et al. 2011

J. Clin. Invest.

236

165

View full text Add to dashboard Cite

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“…In adults, the liver and gut have distinct endothelial phenotypes whereby vascular adhesion protein 1 (VAP-1) expressed on hepatic sinusoids is implicated in lymphocyte recruitment to the liver, and similarly mucosal addressin cell adhesion molecule 1 (MAdCAM-1) and the chemokine CCL25 are expressed on intestinal mucosal vessels where they are involved in the recruitment of lymphocytes expressing the integrin α4β7 and chemokine receptor CCR9. However, VAP-1 expression becomes induced on mesenteric vessels in IBD, whereas MAdCAM-1 and CCL25 are increased on hepatic endothelium in PSC where they support the recruitment and adhesion of α4β7 hi CCR9 + intestinal mucosal lymphocytes [Adams et al 2008]. As well as being an adhesion molecule, VAP-1 is an enzyme possessing amine oxidase activity, and deamination of the dietary constituent methylamine by VAP-1 has been recently shown to induce the expression of functional MAdCAM-1 on hepatic endothelium in the presence of TNFα [Liaskou et al 2011].…”

Section: Antibioticsmentioning

confidence: 99%

Treatment of autoimmune liver disease: current and future therapeutic options

Trivedi

Hirschfield

2013

Therapeutic Advances in Chronic Disease

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Autoimmune liver disease spans three predominant processes, from the interface hepatitis of autoimmune hepatitis to the lymphocytic cholangitis of primary biliary cirrhosis, and finally the obstructive fibrosing sclerotic cholangiopathy of primary sclerosing cholangitis. Although all autoimmune in origin, they differ in their epidemiology, presentation and response to immunosuppressive therapy and bile acid based treatments. With an ongoing better appreciation of disease aetiology and pathogenesis, treatment is set ultimately to become more rational. We provide an overview of current and future therapies for patients with autoimmune liver disease, with an emphasis placed on some of the evidence that drives current practice.

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“…For example, while CCL25 and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) are expressed in the gut endothelial cells, VAP is expressed in hepatic endothelial cells. CCR9 and integrin α4β7 receptor containing lymphocytes are attracted toward ligands CCL25 and MAdCAM-1 in the intestine, while VAP-1 binds to the liver VAP [8,30,31]. Such a well organized trafficking fails in many inflammatory and autoimmune diseases as such as CeD and IBD, where MAdCAM-1, CCL25, or VAP-1 are expressed non-selectively on both the intestine and the liver.…”

mentioning

confidence: 99%

“…Both the small intestine and the liver are equipped with immune systems and are capable of working as a single unit of immunological defense and they cross talk with each other, when needed [7,8]. This crosstalk between liver and intestine is the backbone of the "Gut-liver" axis and…”

mentioning

confidence: 99%

“…In physiological conditions, the antigens pass through the M cells over the ileal Peyer's patches and are then transported to the mucosal lymphoid follicles or the mesenteric lymph nodes, where the lymphocytes are presented these antigens to T-cells. These activated lymphocytes then express various receptors, as chemokine receptor CCR9, integrin α4β7, or vascular adhesion protein-1 (VAP-1) [8,30,31]. These lymphocytes undergo pre-programmed specific homing either to the intestine or liver, based on the specific ligands expressed in the organs for these receptors.…”

mentioning

confidence: 99%

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Gut-liver axis and disease infidelity: A subject worth exploring

Das

Makharia

2014

Indian J Gastroenterol

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The spectrum of gluten-related disorders is widening and varies from celiac disease (CeD) to non-celiac gluten sensitivity [1]. While small intestine was thought to be the only organ involved in patients with CeD, it is now recognized that the hypersensitivity to gluten is not limited to the small intestine alone and may affect other organs such as skin, brain, and bones independent of intestinal involvement [2][3][4][5]. Dermatitis herpetiformis and gluten ataxia are the best example of such phenomena.In a study published in this issue of the Journal, Maiwall et al. [6] have reported small intestinal changes in 61 patients with cryptogenic chronic liver disease (cryptogenic chronic liver disease 47 and 14 biopsy proven noncirrhotic idiopathic portal hypertension) and 59 patients with hepatitis B or hepatitis C virus related cirrhosis as controls. All of them were screened for CeD using anti-tissue transglutaminase antibody (anti-tTG Ab) and patients having a positive screening test were invited for upper gastrointestinal endoscopy and duodenal biopsies were obtained from them. CeD was diagnosed on the basis of combination of a positive serology and presence of villous abnormalities. An unexpectedly high number of both study subjects (40, 66 %) and controls (17, 29 %) were detected to have a positive anti-tTG Ab. Of them, 37 in the study group and 11 in control group underwent duodenal biopsies, respectively. Overall, six patients fulfilled the criteria for the diagnosis of CeD (including two patients with noncirrhotic intrahepatic portal hypertension [NCIPH]) as compared to none in controls.Additionally, a significant number of both study subject controls also had villous abnormalities (various grade of villous atrophy, crypt hyperplasia, and chronic inflammatory cells in the lamina propria, these changes however were not accompanied by rise in intraepithelial lymphocytes. Such changes were seen more often in cryptogenic cirrhosis than those with cirrhosis due to hepatitis B virus or hepatitis C virus-related cirrhosis. Of patients with negative anti-tTG antibody who underwent duodenal biopsies, 4/16 (25 %) of cases and 4/22 (18 %) of controls also showed the presence of villous abnormalities. Furthermore, after observing a high anti-tTG Ab positive in both study group (cryptogenic cirrhosis) and controls (cirrhosis due to HBV or HCV), the authors retested the serum samples by two different ELISA kits procured from two different manufacturers and showed also remarkable variability in the performance of ELISA kits. The anti-tTG antibody was positive in 16 (31 %) cases and in 15 (38 %) controls by a kit obtained from Euroimmune and in 12 (23 %) cases and 8 (20 %) controls using kits obtained from Inova.While Maiwall et al. in the present study have shown that approximately 10 % of cryptogenic cirrhosis have coexistent CeD, more importantly, they raise an important question. Is there a causal relationship between CeD and liver damage, and if so, then how? They also highlighted two another issues. Firstly, that man...

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Immunology of the gut and liver: a love/hate relationship

Cited by 63 publications

References 160 publications

Mice overexpressing BAFF develop a commensal flora–dependent, IgA-associated nephropathy

Mice overexpressing BAFF develop a commensal flora–dependent, IgA-associated nephropathy

Treatment of autoimmune liver disease: current and future therapeutic options

Gut-liver axis and disease infidelity: A subject worth exploring

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