ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015
IKKα is required for the homeostasis of regulatory T cells and for the expansion of both regulatory and effector CD4 T cells.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- Single-Cell Analyses Reveal IKKα Regulates the Interaction Between Macrophages and T Cells in the Doxorubicin-Induced Cardiomyopathy.Inflammation · 2026Article
- NF-κB regulated expression of A20 controls IKK dependent repression of RIPK1 induced cell death in activated T cells.Cell death and differentiation · 2025Article
- Functional CRISPR screens in T cells reveal new opportunities for cancer immunotherapies.Molecular cancer · 2024Review
- Interferon autoantibodies as signals of a sick thymus.Frontiers in immunology · 2024Review
- Bivalent structure of a TNFR2-selective and agonistic TNF-α mutein Fc-fusion protein enhances the expansion activity of regulatory T cells.Scientific reports · 2023Article
- Pparα knockout in mice increases the Th17 development by facilitating the IKKα/RORγt and IKKα/Foxp3 complexes.Communications biology · 2023Article
- NF-κB in control of regulatory T cell development, identity, and function.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Article
- NF-κB Inducing Kinase Regulates Intestinal Immunity and Homeostasis.Frontiers in immunology · 2022Review
- Phosphorylation of RIPK1 serine 25 mediates IKK dependent control of extrinsic cell death in T cells.Frontiers in immunology · 2022Article
- A T cell-intrinsic function for NF-κB RelB in experimental autoimmune encephalomyelitis.Scientific reports · 2021Article
- TNF-TNFR2 Signal Plays a Decisive Role in the Activation of CD4Advances in experimental medicine and biology · 2021Article
- The role of CD4International journal of biological sciences · 2021Review
- TNFR2: Role in Cancer Immunology and Immunotherapy.ImmunoTargets and therapy · 2021Review
- Ragweed pollen induces allergic conjunctivitis immune tolerance in miceInternational journal of ophthalmology · 2021Article
- Molecular mechanism for impaired suppressive function of Tregs in autoimmune diseases: A summary of cell-intrinsic and cell-extrinsic factors.Journal of cellular and molecular medicine · 2020Review
- RelB regulates the homeostatic proliferation but not the function of Tregs.BMC immunology · 2020Article
- Role of NF-kappaB2-p100 in regulatory T cell homeostasis and activation.Scientific reports · 2019Article
- Article
- Editorial: The Role of TNF-TNFR2 Signal in Immunosuppressive Cells and Its Therapeutic Implications.Frontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
It was reported that TNF receptor type II signaling, which has the capacity to stimulate CD4+ forkhead box P3+ (Foxp3+) regulatory T cells (Tregs), activated the noncanonical NF-κB pathway in an IKKα-dependent manner. Therefore, we studied the role of IKKα in the homeostasis of Treg population. To this end, we generated a mouse strain with conditional knockout of IKKα in CD4 cells (Ikkα(f/f):CD4.Cre) that showed a >60% reduction in the number of Tregs in the thymus and peripheral lymphoid tissues, whereas the number of Foxp3- effector T cells (Teffs) remained at a normal level. The function of Tregs deficient in IKKα was examined using Rag1(-/-) mice cotransferred with naive CD4 cells (nCD4s). Although wild-type (WT) Tregs inhibited colitis induced by transfer of WT nCD4s, IKKα-deficient Tregs failed to do so, which was associated with their inability to reconstitute Rag1(-/-) mice. Furthermore, nCD4s deficient in IKKα also failed to reconstitute Rag1(-/-) mice and were defective in proliferative responses in vitro and in vivo. Thus, our study reveals a novel role of IKKα in the maintenance of a normal Treg population and in the control of expansion of CD4 T cells. These properties of IKKα may be exploited as therapeutic strategies in the treatment of major human diseases.
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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.