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IL-17-producing ?? T cells switch migratory patterns between resting and activated states.

ABSTRACT: Interleukin 17-producing ?? T (??T17) cells have unconventional trafficking characteristics, residing in mucocutaneous tissues but also homing into inflamed tissues via circulation. Despite being fundamental to ??T17-driven early protective immunity and exacerbation of autoimmunity and cancer, migratory cues controlling ??T17 cell positioning in barrier tissues and recruitment to inflammatory sites are still unclear. Here we show that ??T17 cells constitutively express chemokine receptors CCR6 and CCR2. While CCR6 recruits resting ??T17 cells to the dermis, CCR2 drives rapid ??T17 cell recruitment to inflamed tissues during autoimmunity, cancer and infection. Downregulation of CCR6 by IRF4 and BATF upon ??T17 activation is required for optimal recruitment of ??T17 cells to inflamed tissue by preventing their sequestration into uninflamed dermis. These findings establish a lymphocyte trafficking model whereby a hierarchy of homing signals is prioritized by dynamic receptor expression to drive both tissue surveillance and rapid recruitment of ??T17 cells to inflammatory lesions.

SUBMITTER: McKenzie DR

PROVIDER: S-EPMC5465362 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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IL-17-producing γδ T cells switch migratory patterns between resting and activated states.

McKenzie Duncan R DR Kara Ervin E EE Bastow Cameron R CR Tyllis Timona S TS Fenix Kevin A KA Gregor Carly E CE Wilson Jasmine J JJ Babb Rachelle R Paton James C JC Kallies Axel A Nutt Stephen L SL Brüstle Anne A Mack Matthias M Comerford Iain I McColl Shaun R SR

Nature communications 20170605

Interleukin 17-producing γδ T (γδT17) cells have unconventional trafficking characteristics, residing in mucocutaneous tissues but also homing into inflamed tissues via circulation. Despite being fundamental to γδT17-driven early protective immunity and exacerbation of autoimmunity and cancer, migratory cues controlling γδT17 cell positioning in barrier tissues and recruitment to inflammatory sites are still unclear. Here we show that γδT17 cells constitutively express chemokine receptors CCR6 a ...[more]

PMID: 28580944

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Project description:BackgroundVision loss in patients with wet/exudative age-related macular degeneration (AMD) is associated with choroidal neovascularization (CNV), and AMD is the leading cause of irreversible vision impairment in older adults. Interleukin-17A (IL-17A) is a component of the microenvironment associated with some autoimmune diseases. Previous studies have indicated that wet AMD patients have elevated serum IL-17A levels. However, the effect of IL-17A on AMD progression needs to be better understood. We aimed to investigate the role of IL-17A in a laser-induced CNV mouse model.MethodsWe established a laser-induced CNV mouse model in wild-type (WT) and IL-17A-deficient mice and then evaluated the disease severity of these mice by using fluorescence angiography. We performed enzyme-linked immunosorbent assay (ELISA) and fluorescence-activated cell sorting (FACS) to analyze the levels of IL-17A and to investigate the immune cell populations in the eyes of WT and IL-17A-deficient mice. We used ARPE-19 cells to clarify the effect of IL-17A under oxidative stress.ResultsIn the laser-induced CNV model, the CNV lesions were larger in IL-17A-deficient mice than in WT mice. The numbers of γδ T cells, CD3+CD4+RORγt+ T cells, Treg cells, and neutrophils were decreased and the number of macrophages was increased in the eyes of IL-17A-deficient mice compared with WT mice. In WT mice, IL-17A-producing γδ T-cell numbers increased in a time-dependent manner from day 7 to 28 after laser injury. IL-6 levels increased and IL-10, IL-24, IL-17F, and GM-CSF levels decreased in the eyes of IL-17A-deficient mice after laser injury. In vitro, IL-17A inhibited apoptosis and induced the expression of the antioxidant protein HO-1 in ARPE-19 cells under oxidative stress conditions. IL-17A facilitated the repair of oxidative stress-induced barrier dysfunction in ARPE-19 cells.ConclusionsOur findings provide new insight into the protective effect of IL-17A in a laser-induced CNV model and reveal a novel regulatory role of IL-17A-producing γδ T cells in the ocular microenvironment in wet AMD.

Dataset Information

IL-17-producing ?? T cells switch migratory patterns between resting and activated states.

Publications

IL-17-producing γδ T cells switch migratory patterns between resting and activated states.

Similar Datasets

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