Distinct roles for Blimp-1 in autoreactive CD4 T cells during priming and effector phase of autoimmune encephalomyelitis

Aqel, S.; Granitto, Marissa; Nuro-Gyina, Patrick Kwadwo; Pei, Wei; Liu, Yue; Lovett-Racke, Amy E.; Racke, Michael K.; Yang, Yuhong

doi:10.1016/j.jneuroim.2018.10.007

Cited by 3 publications

(1 citation statement)

References 60 publications

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“…However, using a different knockout model for Blimp-1 expression in T cells, other work found an uncontrolled Th17 cell-driven central nervous system pathology in Blimp-1 deficient mice [165]. This controversy may reflect the fact that Blimp-1 seems to play distinct roles during the priming and the effector phase of EAE, as other work found delayed EAE onset but enhanced disease severity during the effector phase in Blimp-1 conditional knockout mice [166].…”

Section: Blimp-1mentioning

confidence: 99%

Decoding IL-23 Signaling Cascade for New Therapeutic Opportunities

Pastor-Fernández

Mariblanca

Navarro

2020

Cells

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The interleukin 23 (IL-23) is a key pro-inflammatory cytokine in the development of chronic inflammatory diseases, such as psoriasis, inflammatory bowel diseases, multiple sclerosis, or rheumatoid arthritis. The pathological consequences of excessive IL-23 signaling have been linked to its ability to promote the production of inflammatory mediators, such as IL-17, IL-22, granulocyte-macrophage colony-stimulating (GM-CSF), or the tumor necrosis factor (TNFα) by target populations, mainly Th17 and IL-17-secreting TCRγδ cells (Tγδ17). Due to their pivotal role in inflammatory diseases, IL-23 and its downstream effector molecules have emerged as attractive therapeutic targets, leading to the development of neutralizing antibodies against IL-23 and IL-17 that have shown efficacy in different inflammatory diseases. Despite the success of monoclonal antibodies, there are patients that show no response or partial response to these treatments. Thus, effective therapies for inflammatory diseases may require the combination of multiple immune-modulatory drugs to prevent disease progression and to improve quality of life. Alternative strategies aimed at inhibiting intracellular signaling cascades using small molecule inhibitors or interfering peptides have not been fully exploited in the context of IL-23-mediated diseases. In this review, we discuss the current knowledge about proximal signaling events triggered by IL-23 upon binding to its membrane receptor to bring to the spotlight new opportunities for therapeutic intervention in IL-23-mediated pathologies.

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Section: Blimp-1mentioning

confidence: 99%

Decoding IL-23 Signaling Cascade for New Therapeutic Opportunities

Pastor-Fernández

Mariblanca

Navarro

2020

Cells

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IL-21 enhances STAT3/Blimp-1 signaling pathway in B cells and contributes to plasma cell differentiation in newly diagnosed patients with myasthenia gravis

Huang

et al. 2020

Immunol Res

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Cytotoxic Activity of CD4 T Cells During the Early Stage of Autoimmune Neuroinflammation

Pradella

et al. 2020

Preprint

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1Pathogenic CD4+ T cells are capable of initiating neuroinflammation in experimental 2 autoimmune encephalomyelitis (EAE). However, the precise effector mechanism of these 3 autoaggressive CD4+ T cells is not entirely elucidated. Here, we demonstrated that 4 pathogenic CD4+ T cells, upon autoantigen stimulation, developed a cytotoxic phenotype at 5 the onset of EAE. The cytotoxic activity of pathogenic CD4+ T cells was sufficient to explain 6 the initial myelin lesion. Consistently, CD4+ T cells of peripheral blood (PBMCs) and 7 cerebrospinal fluid (CSF) from relapse-remitting multiple sclerosis (RRMS) patients present an 8 enhancement of the cytotoxic profile in comparison with healthy control (HC). Moreover, 9 cytotoxic CD4+ T cells (CD4-CTLs) are restrained in the PBMCs of Natalizumab-treated RRMS 10 patients. Mechanistically, autoaggressive CD4-CTLs matched the majority of the molecular 11 pathways of effector CD8+ T cells. Altogether, our findings point to potential new targets for 12 monitoring MS diagnosis, treatment, and the development of novel therapeutic avenues. 13

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Distinct roles for Blimp-1 in autoreactive CD4 T cells during priming and effector phase of autoimmune encephalomyelitis

Cited by 3 publications

References 60 publications

Decoding IL-23 Signaling Cascade for New Therapeutic Opportunities

Decoding IL-23 Signaling Cascade for New Therapeutic Opportunities

IL-21 enhances STAT3/Blimp-1 signaling pathway in B cells and contributes to plasma cell differentiation in newly diagnosed patients with myasthenia gravis

Cytotoxic Activity of CD4 T Cells During the Early Stage of Autoimmune Neuroinflammation

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