The CCR6-CCL20 axis in humoral immunity and T-B cell immunobiology

Lee, Adrian Y S; Körner, Heinrich

doi:10.1016/j.imbio.2019.01.005

Cited by 67 publications

(57 citation statements)

References 79 publications

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“…Chemokines constitute a family of structurally related chemotactic cytokines that regulate the recruitment of leucocytes in physiological and inflammatory conditions . CCL20, also known as MIP‐3α or LARC, is an 8‐kDa protein whose gene is mapped to 2q33‐37.…”

Section: Ccl20/ccr6 Axismentioning

confidence: 99%

“…Although dermal dendritic cells and T cells express CCL20 in the psoriatic dermis, the expression of CCL20 is largely confined to the psoriatic epidermis, suggesting that epidermal keratinocytes are the major source of CCL20 production in psoriatic lesions . The infiltrated CD11c + dendritic cells and CD4+ T cells express CCR6 in the psoriatic dermis . In addition, the serum levels of CCL20 are increased in psoriasis …”

Section: Upregulation Of the Ccl20/ccr6 Axis In Psoriasismentioning

confidence: 99%

“…Chemokines constitute a family of structurally related chemotactic cytokines that regulate the recruitment of leucocytes in physiological and inflammatory conditions. [47][48][49] CCL20, also known as MIP-3α or LARC, is an 8-kDa protein whose gene is mapped to 2q33-37. At the tissue and organ level, CCL20 is expressed in peripheral tissues, including the skin, mucosal sites (lung and intestines), liver and thymus.…”

Section: Ccl20/ccr6 Axismentioning

confidence: 99%

“…At the tissue and organ level, CCL20 is expressed in peripheral tissues, including the skin, mucosal sites (lung and intestines), liver and thymus. [47][48][49] While most chemokines bind to multiple receptors, CCL20 has only one known receptor, CCR6. [47][48][49] CCR6 is expressed on dendritic cells and T cells.…”

Section: Ccl20/ccr6 Axismentioning

confidence: 99%

“…[47][48][49] While most chemokines bind to multiple receptors, CCL20 has only one known receptor, CCR6. [47][48][49] CCR6 is expressed on dendritic cells and T cells. 49,50 Importantly, recent standardized immunophenotyping in human immunology projects indicates that CCR6 is a representative marker for circulating Th17 cells.…”

Section: Ccl20/ccr6 Axismentioning

confidence: 99%

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The CCL20 and CCR6 axis in psoriasis

et al. 2019

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Psoriasis is a TNF‐α/IL‐23/IL‐17A–mediated inflammatory skin disease that causes a significant socioeconomic burden in afflicted patients. IL‐17A–producing immune cells, including Th17 cells, are crucial effector cells in the development of psoriasis. IL‐17A stimulates epidermal keratinocytes to produce CCL20, which eventually recruits CCR6 + Th17 cells into the lesional skin. Thus, the CCL20/CCR6 axis works as a driving force that prepares an IL‐17A–rich cutaneous milieu. In this review, we summarize the current research topics on the CCL20/CCR6 axis and the therapeutic intervention of this axis for psoriasis.

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Section: Ccl20/ccr6 Axismentioning

confidence: 99%

Section: Upregulation Of the Ccl20/ccr6 Axis In Psoriasismentioning

confidence: 99%

Section: Ccl20/ccr6 Axismentioning

confidence: 99%

Section: Ccl20/ccr6 Axismentioning

confidence: 99%

Section: Ccl20/ccr6 Axismentioning

confidence: 99%

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The CCL20 and CCR6 axis in psoriasis

et al. 2019

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CCL20 is a novel ligand for the scavenging atypical chemokine receptor 4

Matti

D’Uonnolo

Artinger

et al. 2020

Journal of Leukocyte Biology

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The chemokine CCL20 is broadly produced by endothelial cells in the liver, the lung, in lymph nodes and mucosal lymphoid tissues, and recruits CCR6 expressing leukocytes, particularly dendritic cells, mature B cells, and subpopulations of T cells. How CCL20 is systemically scavenged is currently unknown. Here, we identify that fluorescently labeled human and mouse CCL20 are efficiently taken-up by the atypical chemokine receptor ACKR4. CCL20 shares ACKR4 with the homeostatic chemokines CCL19, CCL21, and CCL25, although with a lower affinity. We demonstrate that all 4 human chemokines recruit -arrestin1 and -arrestin2 to human ACKR4. Similarly, mouse CCL19, CCL21, and CCL25 equally activate the human receptor. Interestingly, at the same chemokine concentration, mouse CCL20 did not recruit -arrestins to human ACKR4. Further cross-species analysis suggests that human ACKR4 preferentially takes-up human CCL20, whereas mouse ACKR4 similarly internalizes mouse and human CCL20. Furthermore, we engineered a fluorescently labeled chimeric chemokine consisting of the N-terminus of mouse CCL25 and the body of mouse CCL19, termed CCL25_19, which interacts with and is taken-up by human and mouse ACKR4. K E Y W O R D SACKR4, atypical chemokine receptor, CCL19, CCL20, CCL21, CCL25, chemokine scavenging, -arrestin

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Role of chemokine systems in cancer and inflammatory diseases

Zhao

2022

MedComm

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Chemokines are a large family of small secreted proteins that have fundamental roles in organ development, normal physiology, and immune responses upon binding to their corresponding receptors. The primary functions of chemokines are to coordinate and recruit immune cells to and from tissues and to participate in regulating interactions between immune cells. In addition to the generally recognized antimicrobial immunity, the chemokine/chemokine receptor axis also exerts a tumorigenic function in many different cancer models and is involved in the formation of immunosuppressive and protective tumor microenvironment (TME), making them potential prognostic markers for various hematologic and solid tumors. In fact, apart from its vital role in tumors, almost all inflammatory diseases involve chemokines and their receptors in one way or another. Modulating the expression of chemokines and/or their corresponding receptors on tumor cells or immune cells provides the basis for the exploitation of new drugs for clinical evaluation in the treatment of related diseases. Here, we summarize recent advances of chemokine systems in protumor and antitumor immune responses and discuss the prevailing understanding of how the chemokine system operates in inflammatory diseases. In this review, we also emphatically highlight the complexity of the chemokine system and explore its potential to guide the treatment of cancer and inflammatory diseases.

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The CCR6-CCL20 axis in humoral immunity and T-B cell immunobiology

Cited by 67 publications

References 79 publications

The CCL20 and CCR6 axis in psoriasis

The CCL20 and CCR6 axis in psoriasis

CCL20 is a novel ligand for the scavenging atypical chemokine receptor 4

Role of chemokine systems in cancer and inflammatory diseases

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