Eosinophils and primary biliary cirrhosis?Stoking the fire?

Neuberger, James

doi:10.1002/hep.510300150

Cited by 17 publications

(5 citation statements)

References 39 publications

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“…23,24 Significantly increased numbers of eosinophils have been reported in PBC livers. 25,26 Our results indicate that anti-LSEC Abs may be one factor responsible for the increased numbers of eosinophils via production of IL-8. MCP-1 belongs to the C-C class of chemokines and binds to the CCR2 chemokine receptor.…”

Section: Discussionmentioning

confidence: 83%

Capillarization of Hepatic Sinusoid by Liver Endothelial Cell-Reactive Autoantibodies in Patients with Cirrhosis and Chronic Hepatitis

Broomé

Uzunel

et al. 2003

The American Journal of Pathology

148

123

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The special features of liver sinusoidal endothelium (LSE) are crucial for normal liver physiology. Cirrhotic livers, especially in primary biliary cirrhosis (PBC), are characterized by transformation of the LSE into a continuous, vascular type. The transformation is important for disease progression and explains some of the pathological hallmarks of the cirrhotic liver. Here, we investigated the presence of liver sinusoidal endothelial cell (LSEC)-reactive autoantibodies (Abs) in the sera of patients with autoimmune liver diseases, and assessed the ability of these Abs to transform LSE into vascular endothelium. Compared to healthy individuals (9%), significantly higher numbers of patients with PBC (59%; P < 0.001) and autoimmune hepatitis (AIH) (32%; P

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Section: Discussionmentioning

confidence: 83%

Capillarization of Hepatic Sinusoid by Liver Endothelial Cell-Reactive Autoantibodies in Patients with Cirrhosis and Chronic Hepatitis

Broomé

Uzunel

et al. 2003

The American Journal of Pathology

148

123

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“…Finally, these studies show that the progression of hepatic fibrosis is significantly attenuated in the absence of IL-5, thus revealing an important role for IL-5 and eosinophils in the pathogenesis of schistosomiasis. Eosinophilic infiltration is seen in a large number of fibrotic diseases, including viral liver diseases (hepatitis C), adverse drug reactions (such as in halothane hepatitis), liver allograft rejection, graft-versushost disease, primary biliary cirrhosis, endomyocardial fibrosis, idiopathic retroperitoneal fibrosis, sclerosing mediastinitis, sclerosing cholangitis, and pulmonary fibrosis (25,26,38). Thus, targeting the activity of IL-5 and/or eosinophils may prove to be beneficial in a wide variety of chronic fibrotic disorders.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-5 (IL-5) Augments the Progression of Liver Fibrosis by Regulating IL-13 Activity

Reiman¹,

Thompson²,

Feng³

et al. 2006

Infect Immun

179

155

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Eosinophils are frequently found in increased numbers in a variety of chronic fibrotic diseases; however, their role in the development of hepatic fibrosis has not been dissected in vivo. Here, we used interleukin-5 (IL-5) knockout (KO) mice to determine whether eosinophils contribute to the progressive liver fibrosis that develops in response to chronic Schistosoma mansoni infection. Although infection intensities were similar in C57BL/6 and IL-5 KO mice, the average size of granulomas was significantly smaller in both acutely and chronically infected IL-5 KO mice. Their granulomas were also completely devoid of eosinophils. In addition, the knockout mice displayed over a 40% reduction in hepatic fibrosis by week 16 postinfection. The reduced fibrosis was associated with increased production of the antifibrotic cytokine gamma interferon. Moreover, although IL-13 production did not decrease consistently in the absence of IL-5, IL-13-triggered responses were substantially reduced in the granulomatous tissues. This was confirmed by analyzing the expression of several genes associated with alternative macrophage activation, including arginase 1, Fizz-1, and YM-1. Importantly, all of these IL-13-regulated genes have been linked with the mechanisms of wound healing and fibrosis. In addition to IL-5 polarizing the antigen-specific CD4 ؉ Th2 cell response, we found that granuloma eosinophils were themselves a significant source of IL-13. Thus, by producing profibrotic mediators and polarizing the Th2 response, these findings illustrate both direct and indirect roles for eosinophils and IL-5 in the pathogenesis of schistosomiasis-induced liver fibrosis. Thus, inhibiting the activity of IL-5 or eosinophils may prove effective for a variety of chronic fibrotic diseases.

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“…Because eosinophil infiltration was already shown in other fibrotic diseases, such as endomyocardial fibrosis, idiopathic retroperitoneal fibrosis and pulmonary fibrosis, targeting eosinophils may prove to be beneficial in a number of other fibrotic implications ( 89 , 140 ). Little is known, however, about the eosinophilic involvement in the development of intestinal fibrosis in IBD.…”

Section: Role Of Eosinophils In Fibrosismentioning

confidence: 99%

Role of Eosinophils in Intestinal Inflammation and Fibrosis in Inflammatory Bowel Disease: An Overlooked Villain?

et al. 2021

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Eosinophils are leukocytes which reside in the gastrointestinal tract under homeostatic conditions, except for the esophagus which is normally devoid of eosinophils. Research on eosinophils has primarily focused on anti-helminth responses and type 2 immune disorders. In contrast, the search for a role of eosinophils in chronic intestinal inflammation and fibrosis has been limited. With a shift in research focus from adaptive to innate immunity and the fact that the eosinophilic granules are filled with inflammatory mediators, eosinophils are becoming a point of interest in inflammatory bowel diseases. In the current review we summarize eosinophil characteristics and recruitment as well as the current knowledge on presence, inflammatory and pro-fibrotic functions of eosinophils in inflammatory bowel disease and other chronic inflammatory conditions, and we identify research gaps which should be covered in the future.

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Eosinophils and primary biliary cirrhosis?Stoking the fire?

Cited by 17 publications

References 39 publications

Capillarization of Hepatic Sinusoid by Liver Endothelial Cell-Reactive Autoantibodies in Patients with Cirrhosis and Chronic Hepatitis

Capillarization of Hepatic Sinusoid by Liver Endothelial Cell-Reactive Autoantibodies in Patients with Cirrhosis and Chronic Hepatitis

Interleukin-5 (IL-5) Augments the Progression of Liver Fibrosis by Regulating IL-13 Activity

Role of Eosinophils in Intestinal Inflammation and Fibrosis in Inflammatory Bowel Disease: An Overlooked Villain?

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