Cutting Edge: GPR35/CXCR8 Is the Receptor of the Mucosal Chemokine CXCL17

Maravillas-Montero, José Luis; Burkhardt, Amanda M.; Hevezi, Peter; Carnevale, Christina; Smit, Martine J.; Zlotnik, Albert

doi:10.4049/jimmunol.1401704

Cited by 123 publications

(177 citation statements)

References 34 publications

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“…This could be explained by decreased migration of T cells from LN and spleen to the CNS, for example, through altered expression of chemokine receptors. However, we did not find changes in the expression of GPR35, one of the proposed receptors for CXCL17 (data not shown). Lack of CD44 expression has also been correlated with a worse outcome of mice in the EAE model, possibly due to cytokine production associated with Th17 cells.…”

Section: Discussionmentioning

confidence: 99%

Cxcl17 -/- mice develop exacerbated disease in a T cell-dependent autoimmune model

Hernández‐Ruiz

Othy

Herrera

et al. 2019

Journal of Leukocyte Biology

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CXCL17 is a homeostatic chemokine in the mucosa known to chemoattract dendritic cells and macrophages but can also be expressed elsewhere under inflammatory conditions. Cxcl17−/− mice have lower numbers of macrophages or dendritic cells in mucosal tissues. CXCL17 is also able to chemoattract suppressor myeloid cells that can recruit regulatory T cells. To explore a possible role of Cxcl17 in T cells, we studied T cell populations from Cxcl17−/− or wild‐type (WT) littermate mice. Cxcl17−/− mice have higher numbers of CD4+ and CD8+ T cells in spleen and lymph nodes (LNs). Upon activation, they produce higher levels of several proinflammatory cytokines and chemokines. Furthermore, a Cxcl17−/− mouse developed exacerbated disease in a T cell‐dependent model of experimental autoimmune encephalomyelitis (EAE). By 18 days after immunization with myelin oligodendrocyte peptide, only 44% of Cxcl17−/− mice were still alive vs. 90% for WT mice. During EAE, Cxcl17−/− mice exhibited higher numbers of lymphoid and myeloid cells in spleen and LNs, whereas they had less myeloid cell infiltration in the CNS. Cxcl17−/− mice also had higher levels of some inflammatory cytokines in serum, suggesting that they may be involved in the poor survival of these mice. Abnormal T cell function may reflect altered myeloid cell migration, or it could be due to altered T cell development in the thymus. We conclude that CXCL17 is a novel factor regulating T cell homeostasis and function.

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Section: Discussionmentioning

confidence: 99%

Cxcl17 -/- mice develop exacerbated disease in a T cell-dependent autoimmune model

Hernández‐Ruiz

Othy

Herrera

et al. 2019

Journal of Leukocyte Biology

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“…Therefore, there is a need to clarify the relevance of these reported effects of ligands at GPR35 and their significant species selectivity in future studies. It has been reported that GPR35 is expressed in CXCL17-responsive monocytes and in the THP-1 monocytoid cell line and may function as a novel chemokine receptor of the mucosal chemokine CXCL17 [33]. Thus, GPR35 function in macrophages/immune cells is pro-inflammatory, and there-fore, its loss in macrophages would be expected to reduce inflammation and promote intestinal regeneration.…”

Section: Discussionmentioning

confidence: 99%

Disruption of GPR35 Exacerbates Dextran Sulfate Sodium-Induced Colitis in Mice

Farooq

Hou

et al. 2018

Dig Dis Sci

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“…CXCL17 is also expressed in malignancy: in hepatocellular carcinoma, CXCL17 was produced mainly by tumor-infiltrating neutrophils and occasionally by the tumor cells (4). The receptor of CXCL17 was recently detected as GPR35/CXCR8, which is expressed in mucosal tissues, including the gastrointestinal tract and lung (5). The ImmGen database indicated that GPR35 is expressed by macrophages, dendritic cells, and granulocytes (5).…”

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confidence: 99%

“…The receptor of CXCL17 was recently detected as GPR35/CXCR8, which is expressed in mucosal tissues, including the gastrointestinal tract and lung (5). The ImmGen database indicated that GPR35 is expressed by macrophages, dendritic cells, and granulocytes (5).…”

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confidence: 99%

CXCL17 Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation by Recruiting Myeloid-Derived Suppressor Cells and Regulatory T Cells

Oka

Sugaya

Takahashi

et al. 2017

The Journal of Immunology

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CXCL17 is expressed in a variety of cancers and promotes tumor progression by recruiting myeloid-derived suppressor cells (MDSCs). MDSCs suppress tumor immunity by attracting regulatory T cells (Tregs) into tumor sites through CCL5. In this study, we examined the role of CXCL17 in skin disorders. CXCL17 mRNA levels in psoriasis skin, but not in lesional skin of atopic dermatitis or cutaneous T cell lymphoma, were significantly higher than those in normal skin. CXCL17 was mainly expressed in the epidermis, and IFN-γ dose-dependently increased CXCL17 expression by human keratinocytes in vitro. As CXCL17 mRNA expression was increased by treatment with imiquimod (IMQ), we examined the effects of CXCL17 in IMQ-induced psoriasis-like skin inflammation. Injection of recombinant CXCL17 into the ear before and during IMQ application decreased ear thickness, inflammatory cytokine expression, and the number of infiltrating cells compared with PBS injection. Flow cytometric analysis and immunofluorescent staining revealed that the numbers of MDSCs, which are CD11b+Gr-1+, and that of Tregs, which are CD4+CD25+, were higher in the ear of the CXCL17-injected mice than in PBS-injected mice. MDSCs, but not Tregs, showed chemotaxis to CXCL17 in vitro. When mice were injected with anti-CCL5 Ab or anti-CCL4 Ab simultaneously with recombinant CXCL17, ear thickness and cytokine expression increased to a similar level of mice treated with PBS and control IgG, suggesting that these chemokines were important for anti-inflammatory effects. Taken together, CXCL17 attenuates IMQ-induced psoriasis-like skin inflammation by recruiting MDSCs and Tregs, which may be important for regulating excessive inflammation in psoriasis skin.

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Cutting Edge: GPR35/CXCR8 Is the Receptor of the Mucosal Chemokine CXCL17

Cited by 123 publications

References 34 publications

Cxcl17 -/- mice develop exacerbated disease in a T cell-dependent autoimmune model

Cxcl17 -/- mice develop exacerbated disease in a T cell-dependent autoimmune model

Disruption of GPR35 Exacerbates Dextran Sulfate Sodium-Induced Colitis in Mice

CXCL17 Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation by Recruiting Myeloid-Derived Suppressor Cells and Regulatory T Cells

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