The role of T cells and interleukin‐17A in Behçet disease

ABSTRACTInterleukin-17A (IL-17A)-producing γδ T cells differentiate in the fetal thymus and reside in the peripheral tissues, such as the lungs of naïve adult mice. We show here that naturally occurring γδ T cells play a protective role in the lung at a very early stage after systemic infection withCandida albicans.Selective depletion of neutrophils byin vivoadministration of anti-Ly6G monoclonal antibody (MAb) impaired fungal clearance more prominently in the lung than in the kidney 24 h after intravenous infection withC. albicans.Rapid and transient production of IL-23 was detected in the lung at 12 h, preceding IL-17A production and the influx of neutrophils, which reached a peak at 24 h after infection. IL-17A knockout (KO) mice showed reduced infiltration of neutrophils concurrently with impaired fungal clearance in the lung after infection. The major source of IL-17A was the γδ T cell population in the lung, and Cδ KO mice showed little IL-17A production and reduced neutrophil infiltration after infection. Early IL-23 production in a TLR2/MyD88-dependent manner and IL-23-triggered tyrosine kinase 2 (Tyk2) signaling were essential for IL-17A production by γδ T cells. Thus, our study demonstrated a novel role of naturally occurring IL-17A-producing γδ T cells in the first line of host defense againstC. albicansinfection.

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The role of infections in Behçet disease and neuro-Behçet syndrome

Autoimmunity Reviews ◽

10.1016/j.autrev.2015.02.009 ◽

2015 ◽

Vol 14 (7) ◽

pp. 609-615 ◽

Cited By ~ 11

Author(s):

Monica Marta ◽

Ernestina Santos ◽

Ester Coutinho ◽

Ana Martins Silva ◽

João Correia ◽

...

Keyword(s):

Behçet Disease ◽

Behcet Disease ◽

Behçet Syndrome ◽

Behcet Syndrome

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Variants of the IFI16 Gene Affecting the Levels of Expression of mRNA Are Associated with Susceptibility to Behçet Disease

The Journal of Rheumatology ◽

10.3899/jrheum.140949 ◽

2015 ◽

Vol 42 (4) ◽

pp. 695-701 ◽

Cited By ~ 9

Author(s):

Lourdes Ortiz-Fernández ◽

José-Raúl García-Lozano ◽

Marco-Antonio Montes-Cano ◽

Marta Conde-Jaldón ◽

Norberto Ortego-Centeno ◽

...

Keyword(s):

Protective Factor ◽

Behçet Disease ◽

Risk Haplotype ◽

Nucleotide Polymorphisms ◽

Behcet Disease ◽

Expression Levels ◽

Transcript Quantification ◽

Allele Specific ◽

Genetically Determined

Objective.Behçet disease (BD) is a multifactorial disease in which infectious agents have been proposed as triggers in genetically predisposed individuals. The aim of our study was to investigate the role of innate immunity receptors, specifically the nucleic acid sensors, in susceptibility to BD.Methods.Seventy-four tag single nucleotide polymorphisms (tSNP) selected in 9 candidate genes (DDX58, IFIH1, TLR3, TLR7, TLR8, AIM2, IFI16, ZBP1, and TLR9) were genotyped in 371 patients and 854 controls. Assays of mRNA expression and allele-specific transcript quantification (ASTQ) were performed in 110 and 50 controls, respectively.Results.Patients and controls were genotyped and 2 tSNP (rs6940 in IFI16 and rs855873 in AIM2) were associated with BD. To confirm this association, these tSNP were genotyped in 850 additional controls, and the total cohort was randomly divided into 2 cohorts. The association of these 2 tSNP with the disease remained in both cohorts. One haplotype (rs6940T-rs855873G) was identified as a risk factor (OR 1.41, 95% CI 1.06–1.86, p = 0.015), and another (rs6940A-rs855873A) as a protective factor (OR 0.65, 95% CI 0.47–0.90, p = 0.009). Samples with the risk haplotype had lower IFI16 expression levels than samples with the protective (0.99 ± 0.29 vs 1.23 ± 0.50, p = 0.022). Consistently, in the ASTQ assays performed with the nonsynonymous rs6940 SNP, the risk allele had lower IFI16 expression levels than the protective (p = 0.027).Conclusion.Our findings suggest association of IFI16, a cytosolic sensor of dsDNA and mediator of the AIM2 inflammasome-dependent pathway, in susceptibility to BD. Differences genetically determined in the levels of this molecule could be the cause of this association.

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Clonally accumulating T cells in the anterior chamber of Behçet disease

American Journal of Ophthalmology ◽

10.1016/s0002-9394(00)00498-0 ◽

2000 ◽

Vol 130 (2) ◽

pp. 243-245 ◽

Cited By ~ 7

Author(s):

Hiroshi Keino ◽

Jun-ichi Sakai ◽

Kusuki Nishioka ◽

Takayuki Sumida ◽

Masahiko Usui

Keyword(s):

T Cells ◽

Anterior Chamber ◽

Behçet Disease ◽

Behcet Disease

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Regulatory T cell/Th17 balance in the pathogenesis of pediatric Behçet disease

Rheumatology ◽

10.1093/rheumatology/keab253 ◽

2021 ◽

Author(s):

Anne Filleron ◽

Tu Anh Tran ◽

Audrey Hubert ◽

Alexia Letierce ◽

Guillaume Churlaud ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Response ◽

Behçet Disease ◽

Inflammatory Disorder ◽

Behcet Disease ◽

Regulatory T Lymphocytes ◽

Hla Dr ◽

Cell Subpopulations ◽

T Cell Subpopulations

Abstract Objectives Behçet disease (BD) is a chronic systemic inflammatory disorder of unknown aetiology. The aim of this study was to determine the orientation of T cell subpopulations in pediatric BD and more precisely to look for a regulatory T lymphocytes (Tregs)/Th17 imbalance. Methods T cell subpopulations were analyzed by flow cytometry in the peripheral blood of pediatric patients with acute (aBD, n = 24), remitting (rBD, n = 12) BD, and in healthy controls (HC, n = 24). Tregs (CD4+CD25hiCD127-/loFoxp3+), activated Tregs (GITR, LAP, CTLA-4, and HLA-DR expression), CD4+ and CD8+ T cells producing interferon-g (Th1 and Tc1) or interleukin (IL)-17 (Th17 and Tc17) under polyclonal (OKT3/IL-2) or antigenic (Streptococcus sanguis KTH-1 peptides and HSP-60) stimulation, were numerated. Results Th17 (1.9 and 5.1 fold) and Tc17 (4.0 and 2.0 fold) frequency under mitogenic stimulation was significantly increased in aBD and rBD patients as compared with HC. Th17 frequency under antigenic stimulation was also higher in patients than in HC. The percentage and number of Tregs and activated Tregs in patients and in HC were similar. However, when Tregs were removed, antigen-driven differentiation into Th1 and Th17 was significantly boosted in BD but not in HC CD4+T cells. Conclusion There is a bias toward a Th17 polarization in acute and remitting BD children. Although we did not observe an increase in the number of Tregs in these patients, their Tregs limit CD4+T cell differentiation into Th1 and Th17 cells. Thus, in pediatric BD, Tregs seem to incompletely counterbalance a Th17 orientation of the helper T cell response.

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Interleukin-17A Promotes CD8+ T Cell Cytotoxicity To Facilitate West Nile Virus Clearance

Journal of Virology ◽

10.1128/jvi.01529-16 ◽

2016 ◽

Vol 91 (1) ◽

Cited By ~ 15

Author(s):

Dhiraj Acharya ◽

Penghua Wang ◽

Amber M. Paul ◽

Jianfeng Dai ◽

David Gate ◽

...

Keyword(s):

T Cells ◽

West Nile Virus ◽

T Cell ◽

Cell Cytotoxicity ◽

West Nile ◽

Viral Burden ◽

Interleukin 17A ◽

Microbial Infections ◽

T Cell Cytotoxicity

ABSTRACT CD8+ T cells are crucial components of immunity and play a vital role in recovery from West Nile virus (WNV) infection. Here, we identify a previously unrecognized function of interleukin-17A (IL-17A) in inducing cytotoxic-mediator gene expression and promoting CD8+ T cell cytotoxicity against WNV infection in mice. We find that IL-17A-deficient (Il17a −/−) mice are more susceptible to WNV infection and develop a higher viral burden than wild-type (WT) mice. Interestingly, the CD8+ T cells isolated from Il17a −/− mice are less cytotoxic and express lower levels of cytotoxic-mediator genes, which can be restored by supplying recombinant IL-17A in vitro and in vivo. Importantly, treatment of WNV-infected mice with recombinant IL-17A, as late as day 6 postinfection, significantly reduces the viral burden and increases survival, suggesting a therapeutic potential for IL-17A. In conclusion, we report a novel function of IL-17A in promoting CD8+ T cell cytotoxicity, which may have broad implications in other microbial infections and cancers. IMPORTANCE Interleukin-17A (IL-17A) and CD8+ T cells regulate diverse immune functions in microbial infections, malignancies, and autoimmune diseases. IL-17A is a proinflammatory cytokine produced by diverse cell types, while CD8+ T cells (known as cytotoxic T cells) are major cells that provide immunity against intracellular pathogens. Previous studies have demonstrated a crucial role of CD8+ T cells in recovery from West Nile virus (WNV) infection. However, the role of IL-17A during WNV infection remains unclear. Here, we demonstrate that IL-17A protects mice from lethal WNV infection by promoting CD8+ T cell-mediated clearance of WNV. In addition, treatment of WNV-infected mice with recombinant IL-17A reduces the viral burden and increases survival of mice, suggesting a potential therapeutic. This novel IL-17A–CD8+ T cell axis may also have broad implications for immunity to other microbial infections and cancers, where CD8+ T cell functions are crucial.

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