CCR6 and NK1.1 distinguish between IL‐17A and IFN‐γ‐producing γδ effector T cells

Haas, Julian; González, Frano H. Malinarich; Schmitz, Susanne; Chennupati, Vijaykumar; Föhse, Lisa; Kremmer, Elisabeth; Förster, Reinhold; Prinz, Immo

doi:10.1002/eji.200939922

Cited by 251 publications

(309 citation statements)

References 53 publications

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“…S6C). Furthermore, in agreement with published reports 45, 46 , we found that control IL-17 producing cells had a significantly higher CD44 MFI than IFNγ producing cells (Fig. S6D).…”

Section: Resultssupporting

confidence: 93%

Integration of T‐cell receptor, Notch and cytokine signals programs mouse γδ T‐cell effector differentiation

Zarin

Chen

et al. 2018

Immunol Cell Biol

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γδ T-cells perform a wide range of tissue and disease specific functions that are dependent on the effector cytokines produced by these cells. However, the aggregate signals required for the development of interferon-γ (IFNγ) and interleukin-17 (IL-17) producing γδ T-cells remain unknown. Here, we define the cues involved in the functional programming of γδ T-cells, by examining the roles of T-cell receptor (TCR), Notch, and cytokine-receptor signaling. KN6 γδTCR-transduced Rag2−/− T-cell progenitors were cultured on stromal cells variably expressing TCR and Notch ligands, supplemented with different cytokines. We found that distinct combinations of these signals are required to program IFNγ versus IL-17 producing γδ T cell subsets, with Notch and weak TCR ligands optimally enabling development of γδ17 cells in the presence of IL-1β, IL-21 and IL-23. Notably, these cytokines were also shown to be required for the intrathymic development of γδ17 cells. Together, this work provides a framework of how signals downstream of TCR, Notch and cytokine receptors integrate to program the effector function of IFNγ and IL-17 producing γδ T-cell subsets.

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“…S6C). Furthermore, in agreement with published reports 45, 46 , we found that control IL-17 producing cells had a significantly higher CD44 MFI than IFNγ producing cells (Fig. S6D).…”

Section: Resultssupporting

confidence: 93%

Integration of T‐cell receptor, Notch and cytokine signals programs mouse γδ T‐cell effector differentiation

Zarin

Chen

et al. 2018

Immunol Cell Biol

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“…42: 1250Immunol. -1260 previously demonstrated [6,34] and characterized as a phenotype of IL-17 producers in the intestine [35]. However, whether the impairment of CCR6 + γδ T-lymphocyte accumulation by anti-CCL25 mAb during allergic pleurisy occurred via a direct mechanism (due to the coexpression with CCR9) or via an indirect mechanism is yet to be defined.…”

Section: Discussionmentioning

confidence: 99%

“…This unique subset of lymphocytes can provide rapid tissue-specific immune responses, without the requirement of antiCorrespondence: Dr. Carmen Penido e-mail: cpenido@far.fiocruz.br gen presentation or clonal expansion, and is able to produce a large repertory of Th1-, Th2-, and Th17-associated cytokines [2][3][4][5][6]. These characteristics make γδ T cells a crucial first line of defense during infection, tissue damage, or stress.…”

Section: Introductionmentioning

confidence: 99%

CCL25 induces α₄β₇ integrin‐dependent migration of IL‐17⁺γδ T lymphocytes during an allergic reaction

Costa¹,

Bornstein²,

Candéa³

et al. 2012

Eur J Immunol

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Herein, we provide evidence that during allergic inflammation, CCL25 induces the selective migration of IL-17 + γδ T cells mediated by α 4 β 7 integrin. Intrapleural injection of CCL25 into ovalbumin (OVA)-immunized C57BL/6 mice triggered the accumulation of γδ T lymphocytes expressing CCR9 (CCL25 receptor) and α 4 β 7 integrin in the pleura, but failed to attract αβ T lymphocytes. CCL25 attracted CCR6 + γδ T cells producing IL-17 (but not IFN-γ or IL-4). OVA challenge triggered increased production of CCL25 followed by the accumulation of CCR9 + , α 4 β 7 + , and CCR6 + /IL-17 + γδ T cells into the pleural cavities of OVA-immunized mice, which was inhibited by the in vivo neutralization of CCL25. The in vivo blockade of α 4 β 7 integrin also inhibited the migration of IL-17 + γδ T lymphocytes (but not of αβ T lymphocytes) into mouse pleura after OVA challenge, suggesting that the CCL25/α 4 β 7 integrin pathway is selective for γδ T cells. In addition, α 4 β 7 integrin blockade impaired the in vitro transmigration of γδ T cells across endothelium (which expresses α 4 β 7 ligands VCAM-1 and MadCAM-1), which was induced by CCL25 and by cell-free pleural washes recovered from OVA-challenged mice. Our results reveal that during an allergic reaction, CCL25 drives IL-17 + γδ T-cell mobilization to inflamed tissue via α 4 β 7 integrin and modulates IL-17 levels. Keywords: Adhesion molecules IntroductionLymphocytes bearing the γδ T-cell receptor (TCR) comprise a minor T-lymphocyte subset in blood and secondary lymphoid tissues and are preferentially localized in epithelial and mucosal tissues [1,2]. This unique subset of lymphocytes can provide rapid tissue-specific immune responses, without the requirement of antiCorrespondence: Dr. Carmen Penido e-mail: cpenido@far.fiocruz.br gen presentation or clonal expansion, and is able to produce a large repertory of Th1-, Th2-, and Th17-associated cytokines [2][3][4][5][6]. These characteristics make γδ T cells a crucial first line of defense during infection, tissue damage, or stress.γδ T cells have been shown to migrate into the airways during allergic inflammation highly controlled by a chemotactic gradient of chemokines produced in tissue [5,[7][8][9][10][11]. We have previously demonstrated that allergen-induced γδ T-cell accumulation is * These authors contributed equally to this work.www.eji-journal.eu Eur. J. Immunol. 2012. 42: 1250-1260 Immunomodulation 1251 paralleled with a marked production of chemokines in the tissue, including CCL25/TECK [11]. CCL25 is mostly described as a homeostatic chemokine that plays a major role in T-cell development in the thymus and in intraepithelial lymphocytes (IELs) homing into small intestine mucosa [12]. Recent data have provided evidence that CCL25 production increases during inflammatory processes that take place at nonmucosal tissues, such as autoimmune arthritis, atherosclerosis, and allergy [11,13,14]. Moreover, we and others have shown that γδ T lymphocytes migrate in vitro toward CCL25, via its counterpart receptor CCR9 [11,...

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“…Although IL‐23R is constitutively expressed on γδ 17 cells, the expression of IL‐1R in peripheral γδ 17 cells is tissue‐dependent 48. In addition to IL‐1R and IL‐23R, the expression of scavenger receptor 2 (Scart 2)49 and CCR6,27 and the lack of CD12225 and CD27 expression26 are often used as markers for γδ 17 cells, with the exception for IL‐17‐producing V γ 1 + γδ T cells 33. These phenotypes, established during thymic development, distinguish γδ 17 cells from IFN‐γ‐producing γδ T ( γδ IFN‐ γ ) cells (Fig.…”

Section: γδ T‐cell Subsets and Their Developmentmentioning

confidence: 99%

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

Akitsu

Iwakura

2018

Immunology

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SummaryInterleukin‐17 (IL‐17) is a pro‐inflammatory cytokine and is involved in the development of many diseases. Recent studies have revealed that IL‐17‐producing γδ T cells (γδ17 cells) in addition to IL‐17‐producing CD4+ T cells [T helper type 17 (Th17) cells] are often the main producers of IL‐17 in mouse models of inflammatory diseases. γδ T cells are functionally committed during intra‐thymic differentiation. γδ thymocytes capable of producing IL‐17, which express the transcription factor retinoic‐acid‐receptor‐related orphan receptor γt and the signature cytokine receptor IL‐23R, leave the thymus, and produce IL‐17 rapidly by the stimulation with IL‐1β and IL‐23 in the periphery. Therefore, γδ17 cells play important roles in the early phase of host defence against pathogens and in inflammatory diseases. γδ T cells that can produce IL‐17 are also increased in the skin of patients with psoriasis and in peripheral blood of patients with ankylosing sclerosis. Indeed, the therapy targeting IL‐17 has been approved or is in clinical trials, and proved to be very efficient to treat psoriasis, psoriatic arthritis and ankylosing sclerosis. In this review, we discuss recent knowledge about the pathophysiological function of γδ17 cells in infection and inflammatory diseases and therapeutic advances targeting IL‐17.

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CCR6 and NK1.1 distinguish between IL‐17A and IFN‐γ‐producing γδ effector T cells

Cited by 251 publications

References 53 publications

Integration of T‐cell receptor, Notch and cytokine signals programs mouse γδ T‐cell effector differentiation

Integration of T‐cell receptor, Notch and cytokine signals programs mouse γδ T‐cell effector differentiation

CCL25 induces α₄β₇ integrin‐dependent migration of IL‐17⁺γδ T lymphocytes during an allergic reaction

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

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CCR6 and NK1.1 distinguish between IL‐17A and IFN‐γ‐producing γδ effector T cells

Cited by 251 publications

References 53 publications

Integration of T‐cell receptor, Notch and cytokine signals programs mouse γδ T‐cell effector differentiation

Integration of T‐cell receptor, Notch and cytokine signals programs mouse γδ T‐cell effector differentiation

CCL25 induces α4β7 integrin‐dependent migration of IL‐17+γδ T lymphocytes during an allergic reaction

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

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CCL25 induces α₄β₇ integrin‐dependent migration of IL‐17⁺γδ T lymphocytes during an allergic reaction