ArticleCellular & molecular immunology2013
CD40 interacts directly with RAG1 and RAG2 in autoaggressive T cells and Fas prevents CD40-induced RAG expression.
Article in Cellular & molecular immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Ocrevus reduces TH40 cells, a biomarker of systemic inflammation, in relapsing multiple sclerosis (RMS) and in progressive multiple sclerosis (PMS).Journal of neuroimmunology · 2023Article
- CD40-targeted peptide proposed for type 1 diabetes therapy lacks relevant binding affinity to its cognate receptor. Reply to Pagni PP, Wolf A, Lo Conte M et al [letter].Diabetologia · 2019Article
- A CD40 targeting peptide prevents severe symptoms in experimental autoimmune encephalomyelitis.Journal of neuroimmunology · 2019Article
- Challenges to Reshape the Future of Type 1 Diabetes Research.The Journal of clinical endocrinology and metabolism · 2018Review
- CD40-mediated signalling influences trafficking, T-cell receptor expression, and T-cell pathogenesis, in the NOD model of type 1 diabetes.Immunology · 2017Article
- Overlooked Mechanisms in Type 1 Diabetes Etiology: How Unique Costimulatory Molecules Contribute to Diabetogenesis.Frontiers in endocrinology · 2017Review
- Th40 cells (CD4+CD40+ Tcells) drive a more severe form of Experimental Autoimmune Encephalomyelitis than conventional CD4 T cells.PloS one · 2017Article
- Of the multiple mechanisms leading to type 1 diabetes, T cell receptor revision may play a prominent role (is type 1 diabetes more than a single disease?).Clinical and experimental immunology · 2016Review
- CD40 in coronary artery disease: a matter of macrophages?Basic research in cardiology · 2016Review
- Platelets promote allergic asthma through the expression of CD154.Cellular & molecular immunology · 2015Article
- A CD40-targeted peptide controls and reverses type 1 diabetes in NOD mice.Diabetologia · 2014Article
- Defining a new biomarker for the autoimmune component of Multiple Sclerosis: Th40 cells.Journal of neuroimmunology · 2014Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
CD4(+) T cells expressing CD40 (Th40 cells) constitute a pathogenic T-cell subset that is necessary and sufficient to transfer autoimmune disease. We have previously demonstrated that CD40 signals peripheral Th40 cells to induce RAG1 and RAG2 expression, proteins necessary for the expression of T-cell receptor (TCR), leading to TCR revision. The dependency of TCR expression in the thymus on RAG proteins has long been known. However, despite numerous publications, there is controversy as to whether TCR expression can be altered in the periphery, post-thymic selective pressures. Therefore, a better understanding of TCR expression in primary peripheral cells is needed. We now show that the CD40 protein itself interacts with RAG1 and RAG2 as well as with Ku70 and translocates to the nucleus in Th40 cells. This indicates that the CD40 molecule is closely involved in the mechanism of TCR expression in the periphery. In addition, Fas signals act as a silencing mechanism for CD40-induced RAGs and prevent CD40 translocation to the nucleus. It will be important to further understand the involvement of CD40 in peripheral TCR expression and how TCR revision impacts auto-antigen recognition in order to effectively target and tolerize autoaggressive T cells in autoimmune disease.
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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.