ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Balance between NF-κB p100 and p52 regulates T cell costimulation dependence.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Astrocytes and the tumor microenvironment inflammatory state dictate the killing of glioblastoma cells by Smac mimetic compounds.Cell death & disease · 2024Article
- β2-Adrenergic Receptor Mediated Inhibition of T Cell Function and Its Implications for CAR-T Cell Therapy.International journal of molecular sciences · 2023Review
- Cellular inhibitor of apoptosis 2 (cIAP2) restricts neuroinflammation during experimental autoimmune encephalomyelitis.Journal of neuroinflammation · 2022Article
- The timing of differentiation and potency of CD8 effector function is set by RNA binding proteins.Nature communications · 2022Article
- Role of NF-kappaB2-p100 in regulatory T cell homeostasis and activation.Scientific reports · 2019Article
- The Alternative NF-κB Pathway in Regulatory T Cell Homeostasis and Suppressive Function.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Constitutive expression of NF-κB inducing kinase in regulatory T cells impairs suppressive function and promotes instability and pro-inflammatory cytokine production.Scientific reports · 2017Article
- Smac mimetics synergize with immune checkpoint inhibitors to promote tumour immunity against glioblastoma.Nature communications · 2017Article
- TNFR2 expression by CD4 effector T cells is required to induce full-fledged experimental colitis.Scientific reports · 2016Article
- c-IAP ubiquitin protein ligase activity is required for 4-1BB signaling and CD8(+) memory T-cell survival.European journal of immunology · 2015Article
- The Transitional Endoplasmic Reticulum ATPase p97 Regulates the Alternative Nuclear Factor NF-κB Signaling via Partial Degradation of the NF-κB Subunit p100.The Journal of biological chemistry · 2015Article
- IKKα is required for the homeostasis of regulatory T cells and for the expansion of both regulatory and effector CD4 T cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- Combined immune deficiency in a patient with a novel NFKB2 mutation.Journal of clinical immunology · 2014Article
- Novel NFKB2 mutation in early-onset CVID.Journal of clinical immunology · 2014Article
- Regulation of T cell receptor complex-mediated signaling by ubiquitin and ubiquitin-like modifications.American journal of clinical and experimental immunology · 2014Review
- A cell-intrinsic requirement for NF-κB-inducing kinase in CD4 and CD8 T cell memory.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Effects of radix curcumae-derived diterpenoid C on Helicobacter pylori-induced inflammation and nuclear factor kappa B signal pathways.World journal of gastroenterology · 2013Article
- c-IAP1 and c-IAP2 redundancy differs between T and B cells.PloS one · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
c-IAP1 and c-IAP2 are ubiquitin protein ligases (E3s) that repress noncanonical NF-κB activation. We have created mice that bear a mutation in c-IAP2 that inactivates its E3 activity and interferes, in a dominant-negative fashion, with c-IAP1 E3 activity (c-IAP2(H570A)). The immune response of these animals was explored by infecting them with the Th1-inducing parasite Toxoplasma gondii. Surprisingly, c-IAP2(H570A) mice succumbed because of T cell production of high levels of proinflammatory cytokines. Unlike naive wild-type (WT) cells, which require signals generated by the TCR and costimulatory receptors to become fully activated, naive c-IAP2(H570A) T cells proliferated and produced high levels of IL-2 and IFN-γ to stimulation via TCR alone. c-IAP2(H570A) T cells had constitutive noncanonical NF-κB activation, and IκB kinase inhibition reduced their proliferation to anti-TCR alone to WT levels but had no effect when costimulation via CD28 was provided. Notably, T cells from nfkb2(-/-) mice, which cannot generate the p52 component of noncanonical NF-κB, were also costimulation independent, consistent with the negative role of this unprocessed protein in canonical NF-κB activation. Whereas T cells from nfkb2(+/-) mice behaved like WT, coexpression of a single copy of c-IAP2(H570A) resulted in cleavage of p100, upregulation of p52, and T cell costimulation independence. Thus, p100 represses and p52 promotes costimulation, and the ratio regulates T cell dependence on costimulatory signals.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.