Interleukin-23 is critical for full-blown expression of a non-autoimmune destructive arthritis and regulates interleukin-17A and RORγt in γδ T cells

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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Faculty Opinions recommendation of γδ T cells producing interleukin-17A regulate adipose regulatory T cell homeostasis and thermogenesis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733074157.793552203 ◽

2018 ◽

Author(s):

Sarah Gaffen

Keyword(s):

T Cells ◽

T Cell ◽

Regulatory T Cell ◽

Γδ T Cells ◽

T Cell Homeostasis ◽

Cell Homeostasis ◽

Interleukin 17A

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Faculty Opinions recommendation of γδ T cells producing interleukin-17A regulate adipose regulatory T cell homeostasis and thermogenesis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733074157.793573524 ◽

2020 ◽

Author(s):

David Wiest ◽

Alejandra Contreras

Keyword(s):

T Cells ◽

T Cell ◽

Regulatory T Cell ◽

Γδ T Cells ◽

T Cell Homeostasis ◽

Cell Homeostasis ◽

Interleukin 17A

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γδ T cells producing interleukin-17A regulate adipose regulatory T cell homeostasis and thermogenesis

Nature Immunology ◽

10.1038/s41590-018-0094-2 ◽

2018 ◽

Vol 19 (5) ◽

pp. 464-474 ◽

Cited By ~ 96

Author(s):

Ayano C. Kohlgruber ◽

Shani T. Gal-Oz ◽

Nelson M. LaMarche ◽

Moto Shimazaki ◽

Danielle Duquette ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Regulatory T Cell ◽

Γδ T Cells ◽

T Cell Homeostasis ◽

Cell Homeostasis ◽

Interleukin 17A

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Author Correction: γδ T cells producing interleukin-17A regulate adipose regulatory T cell homeostasis and thermogenesis

Nature Immunology ◽

10.1038/s41590-019-0330-4 ◽

2019 ◽

Vol 20 (3) ◽

pp. 373-373

Author(s):

Ayano C. Kohlgruber ◽

Shani T. Gal-Oz ◽

Nelson M. LaMarche ◽

Moto Shimazaki ◽

Danielle Duquette ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Regulatory T Cell ◽

Γδ T Cells ◽

T Cell Homeostasis ◽

Cell Homeostasis ◽

Interleukin 17A

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γδ T Cells Enhance Autoimmunity by Restraining Regulatory T Cell Responses via an Interleukin-23-Dependent Mechanism

Immunity ◽

10.1016/j.immuni.2010.08.013 ◽

2010 ◽

Vol 33 (3) ◽

pp. 351-363 ◽

Cited By ~ 179

Author(s):

Franziska Petermann ◽

Veit Rothhammer ◽

Malte C. Claussen ◽

Jan D. Haas ◽

Lorena Riol Blanco ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Regulatory T Cell ◽

Γδ T Cells ◽

T Cell Responses ◽

Cell Responses ◽

Interleukin 23 ◽

Dependent Mechanism

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Interleukin-23 instructs protective multifunctional CD4 T cell responses after immunization with the Mycobacterium tuberculosis subunit vaccine H1 DDA/TDB independently of interleukin-17A

Journal of Molecular Medicine ◽

10.1007/s00109-021-02100-3 ◽

2021 ◽

Author(s):

Kristina Ritter ◽

Jochen Behrends ◽

Hanna Erdmann ◽

Jasmin Rousseau ◽

Alexandra Hölscher ◽

...

Keyword(s):

T Cells ◽

Mycobacterium Tuberculosis ◽

Immune Responses ◽

Subunit Vaccine ◽

Effector Memory ◽

List Type ◽

Double Positive ◽

Independent Manner ◽

Interleukin 17A ◽

Interleukin 23

Abstract Interleukin (IL)-17A-producing T helper (Th)17 cells are increasingly being acknowledged to be associated with protective immunity to Mycobacterium tuberculosis (Mtb). Subunit vaccines potently promote protective immune responses against Mtb infection that correlate with an expansion of IL-23-dependent Th17 cells. Previous studies revealed that after vaccination, IL-23 is required for protection against challenge with Mtb but the underlying IL-23-dependent—and possibly IL-17A-mediated—mechanisms remain elusive. Therefore, we here analyzed the early outcome of Mtb infection in C57BL/6, IL-23p19-deficient (−/−), and IL-17A−/− mice after vaccination with the subunit vaccine H1-DDA/TDB to investigate the role of the IL-23-Th17 immune axis for the instruction of vaccine-induced protection. While in IL-23p19−/− mice the protective effect was reduced, protection after vaccination was maintained in IL-17A−/− animals for the course of infection of 6 weeks, indicating that after vaccination with H1-DDA/TDB early protection against Mtb is—although dependent on IL-23—not mediated by IL-17A. In contrast, IL-17A deficiency appears to have an impact on maintaining long-term protection. In fact, IL-23 instructed the vaccine-induced memory immunity in the lung, in particular the sustained expansion of tumor necrosis factor (TNF)+IL-2+ multifunctional T cells, independently of IL-17A. Altogether, a targeted induction of IL-23 during vaccination against Mtb might improve the magnitude and quality of vaccine-induced memory immune responses. Key messages After subunit Mtb vaccination with H1-DDA/TDB, IL-23 but not IL-17A contributes to vaccine-induced early protection against infection with Mtb. IL-17F does not compensate for IL-17A deficiency in terms of H1-DDA/TDB-induced protection against Mtb infection. IL 23 promotes the H1-DDA/TDB-induced accumulation of effector memory T cells independently of IL 17A. IL-23 arbitrates the induction of H1-specific IFN-γ−TNF+IL-2+ double-positive multifunctional CD4 T cells after subunit Mtb vaccination in an IL-17A-independent manner. Graphical abstract

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Two Types of Interleukin 17A–Producing γδ T Cells in Protection Against Pulmonary Infection WithKlebsiella pneumoniae

The Journal of Infectious Diseases ◽

10.1093/infdis/jiw443 ◽

2016 ◽

Vol 214 (11) ◽

pp. 1752-1761 ◽

Cited By ~ 15

Author(s):

Tesshin Murakami ◽

Shinya Hatano ◽

Hisakata Yamada ◽

Yoichiro Iwakura ◽

Yasunobu Yoshikai

Keyword(s):

T Cells ◽

Pulmonary Infection ◽

Γδ T Cells ◽

Interleukin 17A

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Baicalin Ameliorates Imiquimod-Induced Psoriasis-Like Inflammation in Mice

Planta Medica ◽

10.1055/a-0622-8242 ◽

2018 ◽

Vol 84 (15) ◽

pp. 1110-1117 ◽

Cited By ~ 7

Author(s):

Chien-Hui Hung ◽

Chien-Neng Wang ◽

Huei-Hsuan Cheng ◽

Jiunn-Wang Liao ◽

Yi-Ting Chen ◽

...

Keyword(s):

Murine Model ◽

Biological Activities ◽

Unmet Need ◽

Γδ T Cells ◽

Skin Inflammation ◽

Skin Lesions ◽

Interleukin 17 ◽

Interleukin 22 ◽

Interleukin 17A ◽

Interleukin 23

AbstractBaicalin is the main flavonoid from the roots of an important medicinal plant, Scutellaria baicalensis, which shows a variety biological activities. Psoriasis is a chronic immune-mediated inflammatory disease that affects the skin. The unmet need of psoriasis is that many patients do not respond adequately to available clinical treatment. In this study, we found that baicalin showed inhibited dermal inflammation in a murine model of psoriasis via topical application of imiquimod. After a 5-day topical imiquimod application, baicalin or the control vehicle cream was to applied to the lesions of BALB/c mice for a further 4 days. The erythema, scaling, and thickness of the epidermal layer significantly improved in the baicalin-treated mice. The levels of interleukin-17A, interleukin-22, interleukin-23, and tumor necrosis factor in the skin significantly decreased after baicalin treatment. Baicalin also inhibited imiquimod-induced interleukin-17A production in skin draining lymph node cells. The infiltration of γδ T cells into the skin lesions induced by imiquimod was also suppressed after baicalin treatment. These results suggest that baicalin inhibited skin inflammation through the inhibition of the interleukin-17/interleukin-23 axis in a murine model of psoriasis.

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