Essential role for CCR6 in certain inflammatory diseases demonstrated using specific antagonist and knockin mice

Robert, Rémy; Ang, Caroline; Sun, Guizhi; Juglair, Laurent; Lim, Ee X.; Mason, Linda J.; Payne, Natalie Lisa; Bernard, Carole; Mackay, Charles R.

doi:10.1172/jci.insight.94821

Cited by 27 publications

(27 citation statements)

References 57 publications

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“…Scratch injury upregulates the gene expression of CCL20, CXCL8, and IL36G, which may be related to the scratch-induced Koebner phenomenon frequently observed in patients with psoriasis [201]. Preclinical studies have revealed that the humanized anti-CCR6 antibody efficiently inhibits the cutaneous infiltration of CCR6 + T cells in human and murine models [205,206]. The development of small molecule inhibitors against CCR6 is also ongoing [207,208].…”

Section: Il-17a and Cyto/chemokines In Keratinocytesmentioning

confidence: 99%

Interleukin-17A and Keratinocytes in Psoriasis

Furue

Tsuji

et al. 2020

IJMS

150

131

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The excellent clinical efficacy of anti-interleukin 17A (IL-17A) biologics on psoriasis indicates a crucial pathogenic role of IL-17A in this autoinflammatory skin disease. IL-17A accelerates the proliferation of epidermal keratinocytes. Keratinocytes produce a myriad of antimicrobial peptides and chemokines, such as CXCL1, CXCL2, CXCL8, and CCL20. Antimicrobial peptides enhance skin inflammation. IL-17A is capable of upregulating the production of these chemokines and antimicrobial peptides in keratinocytes. CXCL1, CXCL2, and CXCL8 recruit neutrophils and CCL20 chemoattracts IL-17A-producing CCR6+ immune cells, which further contributes to forming an IL-17A-rich milieu. This feed-forward pathogenic process results in characteristic histopathological features, such as epidermal hyperproliferation, intraepidermal neutrophilic microabscess, and dermal CCR6+ cell infiltration. In this review, we focus on IL-17A and keratinocyte interaction regarding psoriasis pathogenesis.

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Section: Il-17a and Cyto/chemokines In Keratinocytesmentioning

confidence: 99%

Interleukin-17A and Keratinocytes in Psoriasis

Furue

Tsuji

et al. 2020

IJMS

150

131

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“…After the success of this trial, a new trial is now ongoing to evaluate the safety, mode of action and clinical efficacy of GSK3050002 in subjects with psoriatic arthritis (https://clinicaltrials.gov/ct2/show/record/NCT02671188). In addition, preclinical study reveals that humanized anti‐CCR6 antibody efficiently inhibits the imiquimod‐induced psoriasiform dermatitis in human CCR6 ‐transgenic/mouse Ccr6 ‐deficient mice . Development of small molecule inhibitors against CCR6 is also ongoing .…”

Section: The Ccl20/ccr6 Axis As Target For the Treatment Of Psoriasismentioning

confidence: 99%

“…In addition, preclinical study reveals that humanized anti-CCR6 antibody efficiently inhibits the imiquimod-induced psoriasiform dermatitis in human CCR6-transgenic/ mouse Ccr6-deficient mice. 75 Development of small molecule inhibitors against CCR6 is also ongoing. 76,77 CCX624 is a potent antagonist for CCR6 and CXCR2.…”

Section: Target For the Treatment Of Psoriasismentioning

confidence: 99%

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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“…CCR6 plays a critical role in the entry of TH17 which is said to induce EAE in the CNS. Direct analysis of CNS-infiltrating cells for CCR6 expression has revealed that in EAE, TH1 cells outnumber TH17 CD4 + and CCR6 is expressed by both subtypes [34,35].…”

Section: Brainmentioning

confidence: 99%

Pleiotropic Immune Functions of Chemokine Receptor 6 in Health and Disease

Ranasinghe¹,

Eri²

2018

Preprint

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Chemokine C-C receptor 6 (CCR6) and its exclusive ligand CCL20 is an extremely important chemokine receptor-ligand pair which controls cell migration and immune induction during inflammatory disease. Not many scientific studies have been undertaken to study its immune mechanisms in detail, but its unique contribution to steady state cell chemotaxis in upholding immune tolerance and regulating immune homeostasis during inflammation is evident in multiple organ systems, including lung, liver, kidney, skin, brain, eye, joints, gonads and the gut in the human body. The role of CCR6 is constitutively expressed as a series of much debilitating severe inflammatory and autoimmune diseases, HIV and cancer metastasis. CD4+ T cells, the central organizers of adaptive immunity, are stringently mobilized by the CCR6/CCL20 axis also induced by cytokines and a host of other factors in a carefully executed immune modulation scenario, to bring about a delicate balance between pro-inflammatory TH17 cells and regulatory Treg cells. Although the exact immune regulatory role is not elucidated yet, CCR6/CCL20 axis is implicated as a front runner which determines the polarization of TH17 and Treg cells and consequently the resolution or progression of many debilitating disorders. This review therefore aims at emphasizing the pleiotropic significance of the chemokines CCR6 and CCL20 in immunologic function in multiple organ systems thereby hoping to accentuate its value in future therapeutic modalities.

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Essential role for CCR6 in certain inflammatory diseases demonstrated using specific antagonist and knockin mice

Cited by 27 publications

References 57 publications

Interleukin-17A and Keratinocytes in Psoriasis

Interleukin-17A and Keratinocytes in Psoriasis

The CCL20 and CCR6 axis in psoriasis

Pleiotropic Immune Functions of Chemokine Receptor 6 in Health and Disease

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