Functional and phenotypic heterogeneity of Th17 cells in health and disease

Byström, Jonas; Clanchy, Felix I. L.; Taher, Taher E.; Al-Bogami, Mohammed M.; Ong, Voon H; Abraham, David; Williams, Richard O.; Mageed, Rizgar A.

doi:10.1111/eci.13032

Cited by 34 publications

(29 citation statements)

References 109 publications

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“…Th17 cells secrete IL-17, IL-22, and GM-CSF, and have a high degree of plasticity (9, 10). They contribute to immunity against fungi and extracellular bacteria, mainly by inducing the release of anti-microbial peptides and attracting myeloid cells to infected mucosal surfaces, especially gut and skin.…”

Section: Effector Cd4+ T Subsetsmentioning

confidence: 99%

HLA-Class II Artificial Antigen Presenting Cells in CD4+ T Cell-Based Immunotherapy

et al. 2019

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CD4 + T cells differentiate into various T helper subsets characterized by distinct cytokine secreting profiles that confer them effector functions adapted to a variety of infectious or endogenous threats. Regulatory CD4 + T cells are another specialized subset that plays a fundamental role in the maintenance of immune tolerance to self-antigens. Manipulating effector or regulatory CD4 + T cells responses is a promising immunotherapy strategy for, respectively, chronical viral infections and cancer, or severe autoimmune diseases and transplantation. Adoptive cell therapy (ACT) is an emerging approach that necessitates defining robust and efficient methods for the in vitro expansion of antigen-specific T cells then infused into patients. To address this challenge, artificial antigen presenting cells (AAPCs) have been developed. They constitute a reliable and easily usable platform to stimulate and amplify antigen-specific CD4 + T cells. Here, we review the recent advances in understanding the functions of CD4 + T cells in immunity and in immune tolerance, and their use for ACT. We also describe the characteristics of different AAPC models and the way to improve their stimulating functions. Finally, we discuss the potential interest of these AAPCs, both as fundamental tools to decipher CD4 + T cell responses and as reagents to generate clinical grade antigen-specific CD4 + T cells for immunotherapy.

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Section: Effector Cd4+ T Subsetsmentioning

confidence: 99%

HLA-Class II Artificial Antigen Presenting Cells in CD4+ T Cell-Based Immunotherapy

et al. 2019

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“…CD4+ Th17 cells are increased in patients with lupus, multiple sclerosis, and severe phenotypes of asthma (16, 17). Th17 cells produce interleukin 17A (IL-17A) leading to increased neutrophil infiltration and inflammation (18, 19).…”

Section: Introductionmentioning

confidence: 99%

“…IL-23 is not required for Th17 cell differentiation. However, IL-23 signaling through the IL-23 receptor (IL-23R) increases IL-17A production and is important in pathogenesis of autoimmune diseases and potentially asthma (17, 24).…”

Section: Introductionmentioning

confidence: 99%

ERα Signaling Increased IL-17A Production in Th17 Cells by Upregulating IL-23R Expression, Mitochondrial Respiration, and Proliferation

Fuseini

Cephus

et al. 2019

Front. Immunol.

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Women have increased prevalence of Th17-mediated autoimmune diseases, including lupus and multiple sclerosis, and severe asthma. While estradiol and progesterone increased IL-17A production in Th17 cells by inhibiting Let7f miRNA expression and increasing IL-23 receptor (IL-23R) expression, it remained unclear how estrogen signaling through the canonical nuclear receptors, estrogen receptor α (ERα) and/or ERβ, regulated this pathway. We hypothesized that estrogen signaling through ERα increased IL-23R expression and IL-17A production from Th17 cells. To test this hypothesis, naïve T cells from WT female, WT male, Esr1−/− and Esr2−/− female mice were differentiated into Th17 cells. IL-17A production and IL-23R expression were significantly increased in Th17 cells from WT female mice compared to Th17 cells from WT male mice. Deletion of ERα (Esr1−/−), but not ERβ (Esr2−/−), significantly decreased IL-17A production and IL-23R expression in Th17 cells by limiting IL-23R expression in a Let-7f dependent manner. ERα deficiency also decreased Th17 cell proliferation as well as decreased T cell metabolism as measured by ATP-linked oxygen consumption rate and proton leakage. Further, we found that Cox20 expression, a protein involved in mitochondrial respiration through assembly of cytochrome c oxidase in the electron transport chain, was increased in Th17 cells from WT female mice compared to Th17 cells from WT male and Esr1−/− female mice. Inhibition of Cox20 decreased IL-17 production in Th17 cells from WT female mice. Combined these studies showed that ERα signaling increased IL-17A production in Th17 cells by upregulating IL-23R expression and promoting mitochondrial respiration and proliferation.

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“…Th17 cells dampen neutrophil function and recruitment but also induce hyperinflammatory responses depending on the immune context (Zelante et al, 2007). There are two known Th17 subsets: pathogenic (GM-CSF producing) Th17 and non-pathogenic (IL-10 producing) Th17 (El-Behi et al, 2011;Bystrom et al, 2019). While advances have been made in defining effector T cell functions during chronic fungal infection, much more work is needed to understand how chronic inflammation alters function.…”

Section: T Cells and Effector Cytokinesmentioning

confidence: 99%

Host Response to Coccidioides Infection: Fungal Immunity

Diep

Hoyer

2020

Front. Cell. Infect. Microbiol.

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Coccidioidomycosis is a fungal, respiratory disease caused by Coccidioides immitis and Coccidioides posadasii . This emerging infectious disease ranges from asymptomatic to pulmonary disease and disseminated infection. Most infections are cleared with little to no medical intervention whereas chronic disease often requires life-long medication with severe impairment in quality of life. It is unclear what differentiates hosts immunity resulting in disease resolution versus chronic infection. Current understanding in mycology-immunology suggests that chronic infection could be due to maladaptive immune responses. Immunosuppressed patients develop more severe disease and mouse studies show adaptive Th1 and Th17 responses are required for clearance. This is supported by heightened immunosuppressive regulatory responses and lowered anti-fungal T helper responses in chronic Coccidioides patients. Diagnosis and prognosis is difficult as symptoms are broad and overlapping with community acquired pneumonia, often resulting in misdiagnosis and delayed treatment. Furthermore, we lack clear biomarkers of disease severity which could aid prognosis for more effective healthcare. As the endemic region grows and population increases in endemic areas, the need to understand Coccidioides infection is becoming urgent. There is a growing effort to identify fungal virulence factors and host immune components that influence fungal immunity and relate these to patient disease outcome and treatment. This review compiles the known immune responses to Coccidioides spp. infection and various related fungal pathogens to provide speculation on Coccidioides immunity.

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Functional and phenotypic heterogeneity of Th17 cells in health and disease

Cited by 34 publications

References 109 publications

HLA-Class II Artificial Antigen Presenting Cells in CD4+ T Cell-Based Immunotherapy

HLA-Class II Artificial Antigen Presenting Cells in CD4+ T Cell-Based Immunotherapy

ERα Signaling Increased IL-17A Production in Th17 Cells by Upregulating IL-23R Expression, Mitochondrial Respiration, and Proliferation

Host Response to Coccidioides Infection: Fungal Immunity

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