Pivotal Role of Dendritic Cell–derived CXCL10 in the Retention of T Helper Cell 1 Lymphocytes in Secondary Lymph Nodes

Yoneyama, Hiroyuki; Narumi, Shosaku; Zhang, Yanyun; Murai, Motohiko; Baggiolini, Marco; Lanzavecchia, Antonio; Ichida, Takafumi; Asakura, Hitoshi; Matsushima, Kouji

doi:10.1084/jem.20011983

Cited by 173 publications

(199 citation statements)

References 39 publications

(136 reference statements)

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“…Important roles of chemokines and their receptors have been demonstrated in inflammation, infection, tissue injury, allergy and cardiovascular diseases as well as in malignant tumors. Chemokine receptor CXCR3 is essential for the physiologic and pathologic recruitment of plasmacytoid dendritic cell precursors, monocytes and natural killer cells to inflamed lymph nodes (LNs) (Cella et al, 1999;Janatpour et al, 2001;Martin-Fontecha et al, 2004), and for retention of Th1 lymphocytes within LNs (Yoneyama et al, 2002). On the other hand, chemokine receptor CCR7 plays a central role in the recruitment of naı¨ve T cells, some memory T cells, and mature dendritic cells to LNs (Cyster, 1999;von Andrian and Mempel, 2003).…”

Section: Introductionmentioning

confidence: 99%

Chemokine receptor CXCR3 promotes colon cancer metastasis to lymph nodes

et al. 2007

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Chemokines and their receptors are essential for leukocyte trafficking, and also implicated in cancer metastasis to specific organs. We have recently demonstrated that CXCR3 plays a critical role in metastasis of mouse melanoma cells to lymph nodes. Here, we show that some human colon cancer cell lines express CXCR3 constitutively. We constructed cells that expressed CXCR3 cDNA ('DLD-1-CXCR3'), and compared with nonexpressing controls by rectal transplantation in nude mice. Although both cell lines disseminated to lymph nodes at similar frequencies at 2 weeks, DLD-1-CXCR3 expanded more rapidly than the control in 4 weeks. In 6 weeks, 59% of mice inoculated with DLD1-CXCR3 showed macroscopic metastasis in para-aortic lymph nodes, whereas only 14% of those with the control (Po0.05). In contrast, metastasis to the liver or lung was rare, and unaffected by CXCR3 expression. In clinical colon cancer samples, we found expression of CXCR3 in 34% cases, most of which had lymph node metastasis. Importantly, patients with CXCR3-positive cancer showed significantly poorer prognosis than those without CXCR3, or those expressing CXCR4 or CCR7. These results indicate that activation of CXCR3 with its ligands stimulates colon cancer metastasis preferentially to the draining lymph nodes with poorer prognosis.

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Section: Introductionmentioning

confidence: 99%

Chemokine receptor CXCR3 promotes colon cancer metastasis to lymph nodes

et al. 2007

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“…Chemokines cause changes in the shape and behavior of the specific cell subpopulations expressing their receptors, leading to chemotaxis (1) toward sites of infection (2) or injury (3,4) and leukocyte activation (5). Together with the differential expression of chemokine receptors, chemokines may determine Th1 vs Th2 response (6).…”

mentioning

confidence: 99%

CpG-A-Induced Monocyte IFN-γ-Inducible Protein-10 Production Is Regulated by Plasmacytoid Dendritic Cell-Derived IFN-α

Blackwell

Krieg

2003

The Journal of Immunology

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Unmethylated CpG motifs in bacterial DNA or synthetic oligodeoxynucleotides (ODN) are known for inducing a Th1 cytokine/chemokine environment, but the mechanisms regulating this have been unclear. Recent studies have defined two classes of CpG ODN, CpG-A ODN that induce plasmacytoid dendritic cells (pDC) to secrete very high levels of IFN-α, and CpG-B ODN that induce only low levels of IFN-α production, but strongly activate B cells. We now demonstrate that a CpG-A ODN directly activates pDC secretion of IFN-α and other soluble factors that secondarily induce purified monocytes to secrete high levels of the Th1-promoting chemokine IFN-γ-inducible protein-10 (IP-10). Cell contact between the monocytes and pDC is not required for this interaction. IFN-α is necessary, but only partially sufficient, for this indirect CpG-induced monocyte IP-10 production. Although CpG ODN induce human PBMC to make only very slight amounts of IFN-γ, we find that these low concentrations synergize with IFN-α for inducing monocyte production of IP-10. These studies provide a better understanding of the mechanisms through which CpG ODN create a Th1-like environment.

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“…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.…”

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confidence: 99%

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

et al. 2005

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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

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Pivotal Role of Dendritic Cell–derived CXCL10 in the Retention of T Helper Cell 1 Lymphocytes in Secondary Lymph Nodes

Cited by 173 publications

References 39 publications

Chemokine receptor CXCR3 promotes colon cancer metastasis to lymph nodes

Chemokine receptor CXCR3 promotes colon cancer metastasis to lymph nodes

CpG-A-Induced Monocyte IFN-γ-Inducible Protein-10 Production Is Regulated by Plasmacytoid Dendritic Cell-Derived IFN-α

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

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