CCR4 Involvement in the Expansion of T Helper Type 17 Cells in a Mouse Model of Psoriasis

Matsuo, Keitaro; Kitahata, Kosuke; Kaibori, Yuichiro; Arima, Yuka; Iwama, Arisa; Ito, Mana; Hara, Yuta; Nagakubo, Daisuke; Quan, Ying‐Shu; Kamiyama, Fumio; Oiso, Naoki; Kawada, Akira; Yoshie, Osamu; Nakayama, Takashi

doi:10.1016/j.jid.2020.12.034

Cited by 14 publications

(14 citation statements)

References 40 publications

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“…Besides CCR10, other chemokine receptors such as CCR6 and CCR4 are also expressed on skin-homing or resident T cells to regulate their localization and function under homeostatic and inflammatory conditions ( Andrew et al., 2001 ; Baekkevold et al., 2005 ; Cai et al., 2011 ; Gray et al., 2011 ; Jiang et al., 2010 ) ( Campbell et al., 2007 ; Casciano et al., 2020 ; Matsuo et al., 2021 ; Puig et al., 2022 ). These chemokine receptors could have redundant functions in directing localization of CCR10 + T cells into the skin in absence of CCL27.…”

Section: Discussionmentioning

confidence: 99%

“…Mice deficient of CCR6 or its ligand CCL20 have reduced skin inflammation in response to the IMQ stimulation ( Campbell et al., 2017 ; Cochez et al., 2017 ; Robert et al., 2017 ; Shi et al., 2021 ; Yu et al., 2019 ), suggesting that in contrast to the CCR10/CCL27 axis, the CCR6/CCL20 axis promotes the skin γδT17 cell activation and tissue inflammation. CCR4 is preferentially expressed in skin Th17 but not γδT17 cells and CCR4-deficient mice also have reduced skin inflammation in response to topical IMQ stimulation ( Matsuo et al., 2021 ). Corroborating with these mouse studies, clinical observations found that expression of CCL17, the ligand of CCR4, and CCL20 is increased, whereas CCL27 is decreased in the lesional skin of psoriatic patients ( Gudjonsson et al., 2010 ; Homey et al., 2000a ; Kim et al., 2014 ; Quaranta et al., 2014 ; Sahmatova et al., 2017 ).…”

Section: Discussionmentioning

confidence: 99%

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CCL27 is a crucial regulator of immune homeostasis of the skin and mucosal tissues

Davila¹,

Xu²,

Huang³

et al. 2022

iScience

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CCL27 is a crucial regulator of immune homeostasis of the skin and mucosal tissues

Davila¹,

Xu²,

Huang³

et al. 2022

iScience

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“…Previously, we have shown that DCs in regional lymph nodes produce CCL22 and attract CCR4-expressing Th17 to enhance DC-Th17 interactions [ 46 , 85 ]. This promotes the expansion of Th17 cells and subsequent induction of CTLs in murine melanoma and psoriasis models [ 13 , 14 ]. Thus, in certain types of cancer, CCR4 may play a role in anti-tumor immunity not only by recruiting Th17 cells into tumor tissues but also by promoting Th17 cell expansion in the draining lymph nodes with subsequent Th17-mediated CTL induction.…”

Section: Th17 Cellmentioning

confidence: 99%

“…While initial studies have suggested protumor activities of Th17 cells, recent studies have demonstrated an important role of Th17 in the induction of CTLs [ 140 , 141 , 142 , 143 ]. Our previous studies have further shown that CCR4 plays an essential role in Th17 expansion and subsequent CTL induction by promoting DC-Th17 interactions in the regional lymph nodes [ 13 , 14 ]. Thus, CCR4 may also substantially contribute to anti-tumor immunity through the expansion of Th17 cells and subsequent induction of tumor-specific CTLs in certain types of cancer.…”

Section: The Chemokine Superfamily As Therapeutic Targets In Cancer Immunotherapymentioning

confidence: 99%

“…Accordingly, some chemokines and their receptors may be involved in the elimination of tumor cells by recruiting anti-tumor effector cells, whereas others may promote tumor progression by attracting immunosuppressive cells. In addition, some chemokines and their receptors are known to play critical roles in the interactions of dendric cells (DCs) and T cells [ 11 , 12 , 13 , 14 ]. Thus, the chemokine superfamily has a multifaceted role in host tumor immunity.…”

Section: Introductionmentioning

confidence: 99%

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Multifaceted Roles of Chemokines and Chemokine Receptors in Tumor Immunity

Matsuo

Yoshie

Nakayama

2021

Cancers

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Various immune cells are involved in host tumor immune responses. In particular, there are many T cell subsets with different roles in tumor immunity. T-helper (Th) 1 cells are involved in cellular immunity and thus play the major role in host anti-tumor immunity by inducing and activating cytotoxic T lymphocytes (CTLs). On the other hand, Th2 cells are involved in humoral immunity and suppressive to Th1 responses. Regulatory T (Treg) cells negatively regulate immune responses and contribute to immune evasion of tumor cells. Th17 cells are involved in inflammatory responses and may play a role in tumor progression. However, recent studies have also shown that Th17 cells are capable of directly inducting CTLs and thus may promote anti-tumor immunity. Besides these T cell subsets, there are many other innate immune cells such as dendritic cells (DCs), natural killer (NK) cells, and myeloid-derived suppressor cells (MDSCs) that are involved in host immune responses to cancer. The migratory properties of various immune cells are critical for their functions and largely regulated by the chemokine superfamily. Thus, chemokines and chemokine receptors play vital roles in the orchestration of host immune responses to cancer. In this review, we overview the various immune cells involved in host responses to cancer and their migratory properties regulated by the chemokine superfamily. Understanding the roles of chemokines and chemokine receptors in host immune responses to cancer may provide new therapeutic opportunities for cancer immunotherapy.

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CCR4⁺CD8⁺ T cells clonally expand to differentiated effectors in murine psoriasis and in human psoriatic arthritis

et al. 2023

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Psoriasis is a chronic inflammatory skin disease with an autoimmune component and associated with joint inflammation in up to 30% of cases. To investigate autoreactive T cells, we developed an imiquimod‐induced psoriasis‐like inflammation model in K5‐mOVA.tg C57BL/6 mice expressing ovalbumin (OVA) on the keratinocyte membrane, adoptively transferred with OT‐I OVA‐specific CD8+ T cells. We evaluated the expansion of OT‐I CD8+ T cells and their localization in skin, blood, and spleen. scRNA‐seq and TCR sequencing data from patients with psoriatic arthritis were also analyzed. In the imiquimod‐treated K5‐mOVA.tg mouse model, OT‐I T cells were markedly expanded in the skin and blood at early time points. OT‐I T cells in the skin showed mainly CXCR3+ effector memory phenotype, whereas in peripheral blood there was an expansion of CCR4+CXCR3+ OT‐I cells. At a later time point, expanded OVA‐specific T‐cell population was found in the spleen. In patients with psoriatic arthritis, scRNA‐seq and TCR sequencing data showed clonal expansion of CCR4+ TCM cells in the circulation and further expansion in the synovial fluid. Importantly, there was a clonotype overlap between CCR4+ TCM in the peripheral blood and CD8+ T‐cell effectors in the synovial fluid. This mechanism could play a role in the generation and spreading of autoreactive T cells to the synovioentheseal tissues in psoriasis patients at risk of developing psoriatic arthritis.

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CCR4 Involvement in the Expansion of T Helper Type 17 Cells in a Mouse Model of Psoriasis

Cited by 14 publications

References 40 publications

CCL27 is a crucial regulator of immune homeostasis of the skin and mucosal tissues

CCL27 is a crucial regulator of immune homeostasis of the skin and mucosal tissues

Multifaceted Roles of Chemokines and Chemokine Receptors in Tumor Immunity

CCR4⁺CD8⁺ T cells clonally expand to differentiated effectors in murine psoriasis and in human psoriatic arthritis

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CCR4 Involvement in the Expansion of T Helper Type 17 Cells in a Mouse Model of Psoriasis

Cited by 14 publications

References 40 publications

CCL27 is a crucial regulator of immune homeostasis of the skin and mucosal tissues

CCL27 is a crucial regulator of immune homeostasis of the skin and mucosal tissues

Multifaceted Roles of Chemokines and Chemokine Receptors in Tumor Immunity

CCR4+CD8+ T cells clonally expand to differentiated effectors in murine psoriasis and in human psoriatic arthritis

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CCR4⁺CD8⁺ T cells clonally expand to differentiated effectors in murine psoriasis and in human psoriatic arthritis