ArticleProceedings of the National Academy of Sciences of the United States of America1998
Differential expression of major histocompatibility complex class II genes on murine macrophages associated with T cell cytokine profile and protective/suppressive effects.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 53 citations in OpenAlex.
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- Pharmacological inhibition of Epac1 protects against pulmonary fibrosis by blocking FoxO3a neddylation.The European respiratory journal · 2025Article
- Whole tissue spatial cellular analysis reveals increased macrophage infiltration in pancreata of autoantibody positive donors and patients with type 1 diabetes.bioRxiv : the preprint server for biology · 2025Article
- Expression of MHC II in DRG neurons attenuates paclitaxel-induced cold hypersensitivity in male and female mice.PloS one · 2024Article
- Baseline gene expression in BALB/c and C57BL/6 peritoneal macrophages influences but does not dictate their functional phenotypes.Experimental biology and medicine (Maywood, N.J.) · 2024Article
- Macrophage-Engineered Vesicles for Therapeutic Delivery and Bidirectional Reprogramming of Immune Cell Polarization.ACS omega · 2021Article
- Dissecting the early steps of MLL induced leukaemogenic transformation using a mouse model of AML.Nature communications · 2020Article
- Class II MHC antigen processing in immune tolerance and inflammation.Immunogenetics · 2019Review
- DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis.Nature communications · 2018Article
- Immune privilege as an intrinsic CNS property: astrocytes protect the CNS against T-cell-mediated neuroinflammation.Mediators of inflammation · 2013Review
- The functional importance of sequence versus expression variability of MHC alleles in parasite resistance.Genetica · 2012Article
- Regulation of major histocompatibility complex class II gene expression, genetic variation and disease.Genes and immunity · 2010Review
- Significance of MHC class II haplotypes and IgG Fc receptors in SLE.Springer seminars in immunopathology · 2006Review
- Cis- and trans-acting gene regulation is associated with osteoarthritis.American journal of human genetics · 2006Article
- An ancient balanced polymorphism in a regulatory region of human major histocompatibility complex is retained in Chinese minorities but lost worldwide.American journal of human genetics · 2006Article
- Dissection of the role of MHC class II A and E genes in autoimmune susceptibility in murine lupus models with intragenic recombination.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
- Discrete gene loci regulate neurodegeneration, lymphocyte infiltration, and major histocompatibility complex class II expression in the CNS.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2003Article
- Widespread bronchogenic dissemination makes DBA/2 mice more susceptible than C57BL/6 mice to experimental aerosol infection with Mycobacterium tuberculosis.Infection and immunity · 2003Article
- Patterned variation in murine MHC promoters.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protective/suppressive major histocompatibility complex (MHC) class II alleles have been identified in humans and mice where they exert a disease-protective and immunosuppressive effect. Various modes of action have been proposed, among them differential expression of MHC class II genes in different types of antigen-presenting cells impacting on the T helper type 1 (Th1)-Th2 balance. To test this possibility, the expression of H-2 molecules from the four haplotypes H-2(b), H-2(d), H-2(k), and H-2(q) was determined on bone marrow-derived macrophages (BMDMs) and splenic B cells. The I-Ab and I-Ek molecules, both well characterized as protective/suppressive, are expressed at a high level on almost all CD11b+ BMDMs for 5-8 days, after which expression slowly declines. In contrast, I-Ad, I-Ak, and I-Aq expression is lower, peaks over a shorter period, and declines more rapidly. No differential expression could be detected on B cells. In addition, the differential MHC class II expression found on macrophages skews the cytokine response of T cells as shown by an in vitro restimulation assay with BMDMs as antigen-presenting cells. The results indicate that macrophages of the protective/suppressive haplotypes express MHC class II molecules at a high level and exert Th1 bias, whereas low-level expression favors a Th2 response. We suggest that the extent of expression of the class II gene gates the back signal from T cells and in this way controls the activity of macrophages. This effect mediated by polymorphic nonexon segments of MHC class II genes may play a role in determining disease susceptibility in humans and mice.
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