Superantigen-Induced Steroid Resistance Depends on Activation of Phospholipase Cβ2

Verhaar, Auke P.; Wildenberg, Manon E.; Duijvestein, Marjolijn; Vos, Anne Christine W.; Peppelenbosch, Maikel P.; Löwenberg, Mark; Hommes, Daniël W.; Brink, Gijs R. van den

doi:10.4049/jimmunol.1202898

Cited by 8 publications

(5 citation statements)

References 18 publications

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“…More specifically, T cell stimulation by bacterial superantigens has been proposed to depend on Gα11 and PLCβ rather than on the TCR-proximal kinase, Lck (87)(88)(89), which was reported to negatively regulate superantigen-mediated responses (90). It will be intriguing to consider how TCR-proximal signalosomes might be differently deployed according to the nature of TCR engagement, although there is strong precedent in B cell biology for differential outcomes being dictated by the form in which antigen is engaged.…”

Section: Superantigen Biology and Innate Signalingmentioning

confidence: 99%

The Innate Biologies of Adaptive Antigen Receptors

Hayday

Vantourout

2020

Annu. Rev. Immunol.

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Nonclonal innate immune responses mediated by germ line–encoded receptors, such as Toll-like receptors or natural killer receptors, are commonly contrasted with diverse, clonotypic adaptive responses of lymphocyte antigen receptors generated by somatic recombination. However, the Variable (V) regions of antigen receptors include germ line–encoded motifs unaltered by somatic recombination, and theoretically available to mediate nonclonal, innate responses, that are independent of or largely override clonotypic responses. Recent evidence demonstrates that such responses exist, underpinning the associations of particular γδ T cell receptors (TCRs) with specific anatomical sites. Thus, TCRγδ can make innate and adaptive responses with distinct functional outcomes. Given that αβ T cells and B cells can also make nonclonal responses, we consider that innate responses of antigen receptor V-regions may be more widespread, for example, inducing states of preparedness from which adaptive clones are better selected. We likewise consider that potent, nonclonal T cell responses to microbial superantigens may reflect subversion of physiologic innate responses of TCRα/β chains.

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Section: Superantigen Biology and Innate Signalingmentioning

confidence: 99%

The Innate Biologies of Adaptive Antigen Receptors

Hayday

Vantourout

2020

Annu. Rev. Immunol.

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“…The glucocorticoid receptor is present in a TCR-associated complex and glucocorticoids rapidly dissociate Lck from the TCR complex, resulting in the inhibition of the canonical Lck- PLC-γ-dependent TCR signaling (Lowenberg et al , 2005, Lowenberg et al , 2006). A recent study showed that staphylococcal enterotoxin B activates a Gαq and PLC-β2-dependent pathway in human T cells, rendering superantigen-stimulated T cells insensitive to glucocorticoids (Verhaar et al , 2013). T cell proliferation induced by PMA and ionomycin, which bypassed the TCR-Lck-PLC-γ signaling, was completely resistant to steroids.…”

Section: Plc-β In Lymphocytesmentioning

confidence: 99%

Phospholipase C-β in immune cells

Kawakami

Xiao

2013

Advances in Biological Regulation

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Great progress has recently been made in structural and functional research of phospholipase C (PLC)-β. We now understand how PLC-β isoforms (β1-β4) are activated by GTP-bound Gαq downstream of G protein-coupled receptors. Numerous studies indicate that PLC-βs participate in the differentiation and activation of immune cells that control both the innate and adaptive immune systems. The PLC-β3 isoform also interplays with tyrosine kinase-based signaling pathways, to inhibit Stat5 activation by recruiting the protein-tyrosine phosphatase SHP-1, with which PLC-β3 and Stat5 form a multi-molecular signaling platform, named SPS complex. The SPS complex has important regulatory roles in tumorigenesis and immune cell activation.

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“…Therefore, we selected 20 and 200 μM (10 X of 20 μM) and assessed the changes in the expression of activation markers on the lymphocytes after T cell stimulation using FCM. As superantigen stimulation induces T cell activation in the presence of GC ( 37 , 45 ), we stimulated PBMCs with TSST-1 in the presence of P4 and/or COR and analyzed the expression of CD25 and PD-1 after 72 h.…”

Section: Resultsmentioning

confidence: 99%

“…Superantigens induce transient T cell activation by T cell receptor (TCR)-major histocompatibility complex (MHC) crosslinking, following anergy induction and regulatory T cell differentiation ( 35 , 36 ). However, superantigens induce a state of steroid resistance in activated T cells by non-canonical pathway ( 37 ). Because we aimed to compare the APC-involved T cell response in the presence of steroids, we selected one of such superantigens, TSST-1 for in vitro stimulation of T cells.…”

Section: Introductionmentioning

confidence: 99%

High-progesterone environment preserves T cell competency by evading glucocorticoid effects on immune regulation

et al. 2022

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Progesterone (P4) and glucocorticoid (GC) play crucial roles in the immunoregulation of a mother to accept and maintain a semi-allogenic fetus. P4 concentration increases during pregnancy and becomes much higher in the placenta than in the other peripheral tissues, wherein the concentration of cortisol (COR), the most abundant GC and a strong immunosuppressor, remains uniform throughout the rest of the body. Here, we evaluated the effect of a high-P4 environment on pregnant immunity by comparing it with COR. Naïve T cell proportion increased transiently in peripheral blood of pregnant women just after delivery and decreased after one month. T cells stimulated with superantigen toxic-shock-syndrome-1 (TSST-1) in the presence of P4 stayed in the naïve state and did not increase, irrespective of the presence of COR, and reactive T cells could not survive. Treatment of T cells with P4 without T cell receptor (TCR) stimulation transiently suppressed T cell activation and proliferation, whereas the levels remain unaltered if P4 was not given before stimulation. Comparison of the engraftment and response against specific antigens using hu-PBL-NOG-hIL-4-Tg mice showed that P4-pretreated lymphocytes preserved CD62L expression and engrafted effectively in the spleen. Moreover, they produced antigen-specific antibodies, whereas COR-pretreated lymphocytes did not. These results suggest that a high-P4 environment suppresses T cell activation and induces T cell migration into lymphoid tissues, where they maintain the ability to produce anti-pathogen antibodies, whereas COR does not preserve T cell function. The mechanism may be pivotal in maintaining non-fetus-specific T cell function in pregnancy.

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Superantigen-Induced Steroid Resistance Depends on Activation of Phospholipase Cβ2

Cited by 8 publications

References 18 publications

The Innate Biologies of Adaptive Antigen Receptors

The Innate Biologies of Adaptive Antigen Receptors

Phospholipase C-β in immune cells

High-progesterone environment preserves T cell competency by evading glucocorticoid effects on immune regulation

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