Macrophage-derived chemokine (MDC)/CCL22 produced by monocyte derived dendritic cells reflects the disease activity in patients with atopic dermatitis

Hashimoto, Shinichi; Nakamura, Koichiro; Oyama, Noritaka; Kaneko, Fumio; Tsunemi, Yuichiro; Saeki, Hidehisa; Tamaki, Kunihiko

doi:10.1016/j.jdermsci.2006.08.004

Cited by 59 publications

(52 citation statements)

References 28 publications

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“…The level of MDC/CCL22 at the tumor site is inversely correlated with PFS, reinforcing its role in the tumor microenvironment. In line with these data, the level of MDC/CCL22 reflects the disease activity in patients with atopic dermatitis (45), an inflammatory skin disease characterized by high serum levels of Th2-type cytokines. Therefore, melanoma developed strategies to simultaneously polarize pDCs to elicit Th2 and immunosuppressive pathways, and to promote the recruitment of pDC-primed T cells that in turn will facilitate tumor progression.…”

Section: Discussionsupporting

confidence: 68%

Plasmacytoid Dendritic Cells Support Melanoma Progression by Promoting Th2 and Regulatory Immunity through OX40L and ICOSL

Aspord

Leccia

Charles

et al. 2013

Cancer Immunology Research

151

153

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Even though melanoma is considered to be one of the most immunogenic solid tumors, handling its development remains a challenge. The basis for such escape from antitumor immune control has not yet been documented. Plasmacytoid dendritic cells (pDC) are emerging as crucial but still enigmatic cells in cancer. In melanoma, the function of tumor-infiltrating pDCs remains poorly explored. We investigated the pathophysiologic role of pDCs in melanoma, both ex vivo from a large cohort of melanoma patients and in vivo in melanoma-bearing humanized mice. pDCs were found in high proportions in cutaneous melanoma and tumor-draining lymph nodes, yet associated with poor clinical outcome. We showed that pDCs migrating to the tumor microenvironment displayed particular features, subsequently promoting proinflammatory Th2 and regulatory immune profiles through OX40L and ICOSL expression. Elevated frequencies of interleukin (IL)-5-, IL-13-and IL-10-producing T cells in patients with melanoma correlated with high proportions of OX40L-and ICOSL-expressing pDCs. Strikingly TARC/CCL17, MDC/CCL22, and MMP-2 found in the melanoma microenvironment were associated with pDC accumulation, OX40L and ICOSL modulation, and/or early relapse. Thus, melanoma actively exploits pDC plasticity to promote its progression. By identifying novel insights into the mechanism of hijacking of immunity by melanoma, our study exposes potential for new therapeutic opportunities. Cancer Immunol Res; 1(6); 402-15. Ó2013 AACR.

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Section: Discussionsupporting

confidence: 68%

Plasmacytoid Dendritic Cells Support Melanoma Progression by Promoting Th2 and Regulatory Immunity through OX40L and ICOSL

Aspord

Leccia

Charles

et al. 2013

Cancer Immunology Research

151

153

View full text Add to dashboard Cite

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“…4). CCL11 and IL-5 are potent inducers of eosinophil development and/or chemotaxis (15), while dendritic cell-produced CCL22 is increased in patients with allergic rhinitis or atopic dermatitis and induces Th2 chemotaxis (41)(42)(43). However, other cytokines might also play a role in the increased eosinophil recruitment and pathology observed in our study.…”

Section: Discussionmentioning

confidence: 71%

Eosinophils Are Recruited in Response to Chitin Exposure and Enhance Th2-Mediated Immune Pathology in Aspergillus fumigatus Infection

O'Dea

Amarsaikhan

et al. 2014

Infect Immun

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In patients infected with the fungus Aspergillus fumigatus, Th1 responses are considered protective, while Th2 responses are associated with increased morbidity and mortality. How host-pathogen interactions influence the development of these protective or detrimental immune responses is not clear. We compared lung immune responses to conidia from two fungal isolates that expressed different levels of the fungal cell wall component chitin. We observed that repeated aspirations of the high-chitinexpressing isolate Af5517 induced increased airway eosinophilia in the lungs of recipient mice compared to the level of eosinophilia induced by isolate Af293. CD4؉ T cells in the bronchoalveolar lavage fluid (BALF) of Af5517-aspirated mice displayed decreased gamma interferon secretion and increased interleukin-4 transcription. In addition, repeated aspirations of Af5517 induced lung transcription of the Th2-associated chemokines CCL11 (eotaxin-1) and CCL22 (macrophage-derived chemokine). Eosinophil recruitment in response to conidial aspiration was correlated with the level of chitin exposure during germination and was decreased by constitutive lung chitinase expression. Moreover, eosinophil-deficient mice subjected to multiple aspirations of Af5517 prior to neutrophil depletion and infection exhibited decreased morbidity and fungal burden compared to the levels of morbidity and fungal burden found in wild-type mice. These results suggest that exposure of chitin in germinating conidia promotes eosinophil recruitment and ultimately induces Th2-skewed immune responses after repeated aspiration. Furthermore, our results suggest that eosinophils should be examined as a potential therapeutic target in patients that mount poorly protective Th2 responses to A. fumigatus infection.

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“…Recent studies have revealed the participation of the CCL17 and CCL22 proteins in diseases such as atopic dermatitis (30) and lymphoma (31). It has been reported that mRNA expression of CCL17 and CCL22 may have an impact on CRC (26).…”

Section: Discussionmentioning

confidence: 99%

Quantification of the chemokines CCL17 and CCL22 in human colorectal adenocarcinomas

Wågsäter

Dienus²,

Löfgren³

et al. 2008

Mol Med Report

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Abstract. Chemokines are believed to play a crucial role in local immunoresponse by regulating leukocyte movement in various tissues, including the intestinal mucosa. It has been suggested that they are key players in cancer biology, and several studies have identified leukocyte infiltration as a hallmark of most cancers. The chemokines CCL17 and CCL22 attract CCR4-bearing cells, which are especially polarised to Th2-type cells and regulatory T cells (Treg). Recent studies have revealed the participation of the CCL17 and CCL22 proteins in diseases such as atopic dermatitis and lymphoma. The purpose of this study was to assess the role of CCL17 and CCL22 protein expression in colorectal cancer (CRC) and to ascertain whether an association exists between promoter -431C>T CCL17 and -961G>A CCL22 gene polymorphisms in CRC versus non-CRC subjects. Using the ELISA assay, we noted a significantly higher expression of CCL22 in tumour tissue with a 2.3-fold up-regulation (tumour vs. paired normal tissue, n=78) but no significant difference in CCL17 protein expression. Immunohistochemistry revealed protein expression of CCL22 and CCL17 in the epithelial compartment of cancer tissue, in epithelial cells at the resection border that reflects normal tissue, and in some stromal cells such as lymphocytes, macrophages, and fibroblasts. Using a TaqMan system we screened for -431C>T CCL17 and -961G>A CCL22 gene variants in 245 CRC patients and 256 controls, but could not find any significant difference in genotype distribution or in allelic frequencies between the two groups. The genotype and allelic distributions of CRC patients were not related to tissue levels of CCL17 and CCL22 protein, and none of the variables were associated with plasma levels or clinical characteristics. To ascertain whether the tissue expression of CCL17 and CCL22 exerts an influence on the pathogenesis of CRC, a forthcoming study on the 5-year survival rate of CRC patients will be conducted. IntroductionChemokines are chemotactic cytokines that participate in the migration of various types of inflammatory cells and play an important role in the local immunoregulation of various tissues, including the intestinal mucosa (1-3). In general, chemokines are thought to be key players in cancer biology (4). Studies have demonstrated that leukocyte infiltration is a hallmark of most cancers (5-7) and promotes and regulates tumour growth, including metastasis and angiogenesis (8,9). T cell infiltration has been shown to be associated with a favourable prognosis in colorectal cancer (CRC) (10,11).The chemokines CCL17 and CCL22 have been the subject of immunogene therapy studies in murine models of colon carcinoma (12). The chemokine CCL17, also referred to as TARC (thymus-and activation-regulated chemokine), is a member of the CC chemokine group that is expressed in the thymus, dendritic cells, endothelial cells, colon tissue, keratinocytes and fibroblasts (13-17). Moreover, CCL17 is a ligand for CC chemokine receptor 4 (CCR4) and attracts CCR4 + cells (18,19). It...

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Macrophage-derived chemokine (MDC)/CCL22 produced by monocyte derived dendritic cells reflects the disease activity in patients with atopic dermatitis

Cited by 59 publications

References 28 publications

Plasmacytoid Dendritic Cells Support Melanoma Progression by Promoting Th2 and Regulatory Immunity through OX40L and ICOSL

Plasmacytoid Dendritic Cells Support Melanoma Progression by Promoting Th2 and Regulatory Immunity through OX40L and ICOSL

Eosinophils Are Recruited in Response to Chitin Exposure and Enhance Th2-Mediated Immune Pathology in Aspergillus fumigatus Infection

Quantification of the chemokines CCL17 and CCL22 in human colorectal adenocarcinomas

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