Regulation by Chemokines of Circulating Dendritic Cell Precursors, and the Formation of Portal Tract–Associated Lymphoid Tissue, in a Granulomatous Liver Disease

Yoneyama, Hiroyuki; Matsuno, Kenjiro; Zhang, Yanyun; Murai, Motohiko; Itakura, Meiji; Ishikawa, Sho; Hasegawa, Go; Naito, Makoto; Asakura, Hitoshi; Matsushima, Kouji

doi:10.1084/jem.193.1.35

Cited by 190 publications

(229 citation statements)

References 48 publications

Supporting

Mentioning

214

Contrasting

Order By: Relevance

“…Two major DC subsets have been identified on the basis of CD8␣ expression, namely CD8␣ ϩ and CD8␣ Ϫ DCs, and much has been studied on the differentiation pathways for these DC subsets (2,6). It has been reported that CD8␣ ϩ DCs, termed ''lymphoid DCs,'' are derived from CD8␣ ϩ CD11c Ϫ precursor cells in the spleen (7), whereas most of CD8␣ Ϫ DCs, termed ''myeloid DCs'', are derived from MHC class II Ϫ CD11c ϩ peripheral blood DC precursors (8,9). Some studies suggest that CD8␣ ϩ DCs produce IL-12 and prime Th1 responses whereas CD8␣ Ϫ DCs prime Th2 responses (10).…”

mentioning

confidence: 99%

Negative regulation of IFN-α/β signaling by IFN regulatory factor 2 for homeostatic development of dendritic cells

Honda

Mizutani

Taniguchi

2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The development and cooperation of distinct subsets of antigenpresenting cells, particularly dendritic cells (DCs), may be critical for maintaining homeostatic immune responses. Recently, much attention has been focused on IFN-␣͞␤, the cytokines induced en masse by virus infection or the activation of Toll-like receptors, in the context of DC activation. Here, we show that mice deficient in IFN regulatory factor 2 exhibit selective loss of CD8␣ ؊ DCs, the so-called myeloid DCs, which is accompanied by a notable increase in CD11c ؊ CD11b high other myeloid lineage cells. Such deficiency is intrinsic to the bone marrow precursors, in which the abnormal induction of IFN-␣͞␤ genes causes excessive IFN signaling. The critical function of IFN regulatory factor 2 in the negative regulation of IFN-␣͞␤ signaling is underscored by the observation that the deficiency is rescued by introducing an additional null mutation for the IFN receptor complex. In view of accumulating evidence of the critical role of IFN-␣͞␤ signaling in DC activation, our present study offers a unique example in that the magnitude of a cytokine signal should be properly balanced in a stage-specific manner during the differentiation and activation of DCs.

show abstract

mentioning

confidence: 99%

Negative regulation of IFN-α/β signaling by IFN regulatory factor 2 for homeostatic development of dendritic cells

Honda

Mizutani

Taniguchi

2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…These inflammatory cells include not only antigen-specific T cells but also nonspecifically activated immune cells. Chemokines and chemokine receptors are known to play an important role in the accumulation of inflammatory cells in liver diseases (Grant et al, 2002;Kusano et al, 2000;Marra et al, 1998;Narumi et al, 1997;Nishioji et al, 2001;Shields et al, 1999;Shimizu et al, 2001;Tamaru et al, 2000;Tsuneyama et al, 2001;Yoneyama et al, 2001). Chemokines such as IFNinducible protein-10, monokine-induced IFN-␥, and macrophage inflammatory protein-1 (MIP-1) have been suggested to play a role in the accumulation of T cells in the human liver of viral hepatitis and autoimmune hepatitis (AIH).…”

mentioning

confidence: 99%

“…In viral hepatitis and autoimmune liver diseases, many inflammatory cells accumulate in the portal tract, which is regarded as the secondary lymphoid tissue (Grant et al, 2002;Yoneyama et al, 2001). These inflammatory cells include not only antigen-specific T cells but also nonspecifically activated immune cells.…”

mentioning

confidence: 99%

Stromal Cell–Derived Factor-1 from Biliary Epithelial Cells Recruits CXCR4-Positive Cells: Implications for Inflammatory Liver Diseases

Terada

Yamamoto

Hakoda

et al. 2003

Laboratory Investigation

View full text Add to dashboard Cite

SUMMARY:Although stromal cell-derived factor-1 (SDF-1) plays an important role in hematopoiesis in the fetal liver, the role after birth remains to be clarified. We investigated the role of SDF-1 and its receptor, CXCR4, in 75 patients; this included controls and patients with viral hepatitis, liver cirrhosis, primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis. Interestingly, SDF-1 appeared up-regulated in biliary epithelial cells (BEC) of inflammatory liver disease. Furthermore, in inflammatory liver diseases, SDF-1 was expressed by BEC of interlobular and septal bile ducts and by proliferated bile ductules. The message expression of SDF-1 in BEC was confirmed at a single-cell level by RT-PCR and laser capture microdissection. The plasma levels of SDF-1 were significantly higher in patients with liver diseases than in normal controls. Flow cytometric analysis of the surface expression of CXCR4 showed that most liver-infiltrating lymphocytes express CXCR4 and the intensity was up-regulated more significantly in liver-infiltrating lymphocytes than in peripheral blood lymphocytes. These results suggest that increased SDF-1 production by BEC may play an important role in the recruitment of CXCR4-positive inflammatory cells into the diseased livers. These data are significant because modulation of the SDF-1/CXCR4 interaction has therapeutic implications for inflammatory liver diseases. (Lab Invest 2003, 83:665-672).

show abstract

“…Yoneyama et al recently reported that P. acnes-induced activation and recruitment of DCs in the liver is an initial event and is a prerequisite for liver injury in this model. 6,7 Furthermore, activated DCs have been shown to move to the hepatic regional lymph nodes (hepatic LNs) and activate P. acnes-specific CD4 ϩ T cells. Those are then recruited to the liver; the result of which is an accumulation of more T cells, macrophages, and DCs producing various chemokines.…”

mentioning

confidence: 99%

CTLA-4Ig suppresses liver injury by inhibiting acquired immune responses in a mouse model of fulminant hepatitis

et al. 2005

View full text Add to dashboard Cite

Expression of costimulatory molecules is significantly upregulated in various organs in an animal model of severe hepatitis induced by injection of Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS). In the present study, we examined whether blockade of costimulatory signals by CTLA-4Ig can suppress the liver injury in this model. We injected an adenovirus encoding CTLA-4Ig (AdCTLA-4Ig) into mice 7 days before, on the same day, or 3 days after P. acnes priming. The virus was found to infect the liver preferentially, and CTLA-4Ig was detected in the serum as early as 2 days after viral injection. After injection of LPS, liver injury and survival rates were examined. Most of the mice not injected with AdCTLA-4Ig died within 12 hours after injection of LPS. In contrast, all the AdCTLA-4Ig-injected mice survived when the virus was injected 7 days before or on the same day as P. acnes priming. Importantly, hemorrhagic liver injury and serum alanine aminotransferase levels were significantly reduced after LPS injection even when AdCTLA-4Ig was injected 3 days after P. acnes priming. Immunological analyses showed that CTLA-4Ig inhibited the activation and expansion of P. acnes-specific CD4 ؉ T cells in the hepatic lymph nodes, leading to a reduction in the recruitment of the cells to the liver. The total amounts of interferon-␥, interleukin-12, and various chemokines in the liver were then decreased, resulting in inhibition of the secondary recruitment of not only T cells but also macrophages. A ntigen presentation to naïve T cells by dendritic cells (DCs) is essential for the activation of antigen-specific T cells, and two signals are known to be necessary for activation. 1 The first signal is from the interaction between the T-cell receptor and antigen peptide-human leukocyte antigen complex, and the second, a costimulatory signal, is from the binding of CD80 or CD86 on DCs and CD28 on T cells. Once activated, T cells express cytotoxic T-lymphocyte antigen-4 (CTLA-4) on their surface, and receive a negative signal through binding with CD80 or CD86 on DCs. 2 CTLA-4 thus acts as a negative feedback molecule in the immune response. 3 CTLA-4Ig is a fusion protein, consisting of the extracellular domain of mouse CTLA-4 and a human immunoglobulin (Ig) Fc fragment. CTLA-4Ig binds to CD80 or CD86 on DCs and induces anergy of antigen-specific T cells through interference with binding between costimulatory molecules on DCs and CD28 on T cells. 4,5 Mice with severe liver injury induced by injection of Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS) is one of the most commonly used animal models of fulminant hepatitis. In this model, all the animals die of liver injury, and there are two different phases in the immune response-a priming phase in which the injection of P. acnes generates granulomas, and an eliciting phase in

show abstract

Regulation by Chemokines of Circulating Dendritic Cell Precursors, and the Formation of Portal Tract–Associated Lymphoid Tissue, in a Granulomatous Liver Disease

Cited by 190 publications

References 48 publications

Negative regulation of IFN-α/β signaling by IFN regulatory factor 2 for homeostatic development of dendritic cells

Negative regulation of IFN-α/β signaling by IFN regulatory factor 2 for homeostatic development of dendritic cells

Stromal Cell–Derived Factor-1 from Biliary Epithelial Cells Recruits CXCR4-Positive Cells: Implications for Inflammatory Liver Diseases

CTLA-4Ig suppresses liver injury by inhibiting acquired immune responses in a mouse model of fulminant hepatitis

Contact Info

Product

Resources

About