IL-17-producing γδT cells are regulated by estrogen during development of experimental arthritis

Andersson, Annica; Grahnemo, Louise; Engdahl, Cecilia; Stubelius, Alexandra; Lagerquist, Marie K; Carlsten, Hans; Islander, Ulrika

doi:10.1016/j.clim.2015.09.014

Cited by 27 publications

(27 citation statements)

References 39 publications

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“…Specifically, TLR4 is considered a pattern-recognition receptor in ALI and is extensively demonstrated to mediate HMGB1-induced lung injury 34, 35 . Liu et al .…”

Section: Discussionmentioning

confidence: 99%

HMGB1-TLR4-IL23-IL17A axis promotes paraquat-induced acute lung injury by mediating neutrophil infiltration in mice

Yan

Chen

et al. 2017

Sci Rep

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Paraquat is a poisoning herbicide that primarily targets lung, leading to severe acute lung injury characterized by extensive neutrophil infiltration. However, the mechanisms underlying the neutrophil infiltration is not clear. In this study, we demonstrated the significance of the signaling cascade from high-mobility group box 1 (HMGB1), to Toll-like receptor 4 (TLR4), interleukin-23 (IL-23), and lastly to IL-17A during the paraquat-induced neutrophil infiltration and the subsequent lung injury in mice. Paraquat challenge significantly elevated serum levels of IL-17A and IL-23, the percentage of IL-17A-producing γδT cells in the lung, and the level of HMGB1 in bronchoalveolar lavage fluid. Reducing IL-17A production using an anti-γδT antibody, targeting IL-23 with the neutralizing antibody against IL-23p19, and blocking HMGB1 signaling by using glycyrrhizin or TLR4−/− mice all dramatically inhibited the infiltration of neutrophils and attenuated lung injury. These novel findings not only reveal the critical role of HMGB1-TLR4-IL-23-IL-17A axis in the pathogenesis of paraquat-induced acute lung injury, but also provide promising therapeutic targets for treating paraquat poisoning.

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“…Specifically, TLR4 is considered a pattern-recognition receptor in ALI and is extensively demonstrated to mediate HMGB1-induced lung injury 34, 35 . Liu et al .…”

Section: Discussionmentioning

confidence: 99%

HMGB1-TLR4-IL23-IL17A axis promotes paraquat-induced acute lung injury by mediating neutrophil infiltration in mice

Yan

Chen

et al. 2017

Sci Rep

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“…Estradiol (E2) treatment of γδ T cells decreased numbers of IL-17+ T cells in the draining lymph nodes, suggested an estradiol mediated regulation of γδ T cell migration from the lymph nodes to various tissues (75). The role of sex hormones on ILC3 function has not been investigated, but is an important area for future studies.…”

Section: Role Of Sex Hormones In Airway Inflammation – Summary Of Animentioning

confidence: 99%

Mechanisms Driving Gender Differences in Asthma

Fuseini

Newcomb

2017

Curr Allergy Asthma Rep

349

226

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Purpose of Review Many phenotypes of asthma exist, ranging from mild asthma with onset during childhood to severe asthma with later onset, making asthma a broad disease with different pathologies. A gender disparity exists in asthma prevalence. As adults, women have an increased asthma prevalence compared to men. Further, women are more likely to have severe asthma and a later onset of asthma compared to men. Here, we review clinical and animal studies that have defined the role of sex hormones in airway inflammation, smooth muscle contraction, mucus production, and airway mechanics associated with asthma pathogenesis. Recent Findings Clinical evidence shows that increased asthma symptoms occur in females starting at puberty compared to boys. However, after puberty, the role for sex hormones in regulating asthma symptoms during menstruation, pregnancy, and menopause is not as clear. Animal studies have shown that estrogen increases and testosterone decreases Th2-mediated airway inflammation, and that females have increased IL-17A-mediated airway inflammation compared to males. Further, females had increased DC and Mφ function compared to males. However, the mechanisms driving the types of allergic inflammation are not fully elucidated. Summary Overall, ovarian hormones increased and testosterone decreased airway inflammation in asthma, but the mechanisms remain unclear. Delineating these pathways using animal models as well as women and men with various phenotypes of asthma will help determine if women with asthma should take (or avoid) hormonal contraceptives as well as predict changes asthma symptoms during life phases, including pregnancy and menopause, when sex hormones are dramatically changing.

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“…These harmful effects include roles in the pathogenesis of autoimmune conditions such as psoriasis, multiple sclerosis, and arthritis, as well as contributions to breast cancer metastasis and bone loss. [3][4][5][6][7] Given that the beneficial and deleterious effects of cd T-cells are largely attributable to the ability of these cells to rapidly produce high levels of inflammatory cytokines, it is important to understand the development and function of the major effector subtypes.…”

Section: Introductionmentioning

confidence: 99%

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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IL-17-producing γδT cells are regulated by estrogen during development of experimental arthritis

Cited by 27 publications

References 39 publications

HMGB1-TLR4-IL23-IL17A axis promotes paraquat-induced acute lung injury by mediating neutrophil infiltration in mice

HMGB1-TLR4-IL23-IL17A axis promotes paraquat-induced acute lung injury by mediating neutrophil infiltration in mice

Mechanisms Driving Gender Differences in Asthma

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

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