ArticleProceedings of the National Academy of Sciences of the United States of America2012
MAPK phosphatase-1 is required for regulatory natural autoantibody-mediated inhibition of TLR responses.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Degalactosylated Whey Protein Suppresses Inflammatory Responses Induced by Lipopolysaccharide in Mice.Frontiers in nutrition · 2022Article
- The Microbiota in Systemic Lupus Erythematosus: An Update on the Potential Function of Probiotics.Frontiers in pharmacology · 2021Review
- Glycan Reactive Natural Antibodies and Viral Immunity.Viral immunology · 2020Review
- Article
- Rheumatoid arthritis patients display B-cell dysregulation already in the naïve repertoire consistent with defects in B-cell tolerance.Scientific reports · 2019Article
- The microbiome in autoimmune diseases.Clinical and experimental immunology · 2019Review
- Autoimmune reactivity to malondialdehyde adducts in systemic lupus erythematosus is associated with disease activity and nephritis.Arthritis research & therapy · 2018Article
- Natural antibodies - facts known and unknown.Central-European journal of immunology · 2018Review
- Impaired CD27Frontiers in immunology · 2018Article
- Modulation of natural IgM autoantibodies to oxidative stress-related neo-epitopes on apoptotic cells in newborns of mothers with anti-Ro autoimmunity.Journal of autoimmunity · 2016Article
- Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients.Scientific reports · 2016Article
- Manipulation of the glycan-specific natural antibody repertoire for immunotherapy.Immunological reviews · 2016Review
- Breakdown of Immune Tolerance in Systemic Lupus Erythematosus by Dendritic Cells.Journal of immunology research · 2016Review
- Apoptotic cell responses in the splenic marginal zone: a paradigm for immunologic reactions to apoptotic antigens with implications for autoimmunity.Immunological reviews · 2016Review
- Protective natural autoantibodies to apoptotic cells: evidence of convergent selection of recurrent innate-like clones.Annals of the New York Academy of Sciences · 2015Review
- The amino acid sensor GCN2 inhibits inflammatory responses to apoptotic cells promoting tolerance and suppressing systemic autoimmunity.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Natural IgM: beneficial autoantibodies for the control of inflammatory and autoimmune disease.Journal of clinical immunology · 2014Review
- Relation of carotid plaque with natural IgM antibodies in patients with systemic lupus erythematosus.Clinical immunology (Orlando, Fla.) · 2014Article
- Article
- TLRs and interferons: a central paradigm in autoimmunity.Current opinion in immunology · 2013Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Naturally arising IgM antibodies, which recognize neo-determinants on apoptotic cell (AC) membranes, are present from birth and can be further induced by AC challenge. Such naturally arising IgM antibodies can suppress proinflammatory responses to purified agonists for Toll-like receptors (TLRs), as well as block the induction of IgG immune complex-induced in vitro and in vivo pathogenic responses. To investigate the responsible mechanisms, we studied the regulatory effects of IgM anti-AC antibody on responses in bone marrow-derived dendritic cells mediated by a range of different TLRs and found that addition of IgM anti-AC inhibited the activation of the primary MAPKs: ERK1/2, JNK, and particularly p38. This was dependent on the recruitment of either C1q or mannose-binding lectin, which are both early complement factors that tag ACs for innate immune recognition. Strikingly, MAPK inhibition of responses to TLR agonists, and to lupus IgG autoantibody-chromatin immune complexes, was found to correlate with, and had an absolute requirement for, the induction and nuclear localization of MAPK phosphatase-1, a factor known to mediate glucocorticoid suppression of immune responses. Further experiments showed that natural IgM antibodies in serum exhibited the same inhibitory properties. These studies elucidate a novel homeostatic pathway by which natural antibodies, which are products of the adaptive immune system, can directly blunt inflammatory responses by recruitment and coordination of a primitive regulatory pathway of the innate immune system.
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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.