ArticleScientific reports2021
HLA-DRB1 allelic epitopes that associate with autoimmune disease risk or protection activate reciprocal macrophage polarization.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
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- AI-enhanced clinical trial-in-a-dish platform for improved DILI risk classification and mechanistic insights into hepatotoxicity.Frontiers in toxicology · 2026Article
- A Genome-Wide Association Study of Hidradenitis Suppurativa from the VA's Million Veteran Program.Dermatology (Basel, Switzerland) · 2026Article
- A Robust Kernel-Based Workflow for Niche Trajectory Analysis.Small methods · 2025Article
- Autoimmune diseases and the risk and prognosis of latent autoimmune diabetes in adults.Diabetologia · 2025Article
- Immune-Related Adverse Events of Checkpoint Inhibitors and Human Leukocyte Antigen System: A Review.ImmunoTargets and therapy · 2025Review
- Macrophages and HLA-Class II Alleles in Multiple Sclerosis: Insights in Therapeutic Dynamics.International journal of molecular sciences · 2024Review
- MHC Class II Presentation in Autoimmunity.Cells · 2023Review
- Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility.Communications biology · 2022Article
- Biomolecular Mechanisms of Autoimmune Diseases and Their Relationship with the Resident Microbiota: Friend or Foe?Pathophysiology : the official journal of the International Society for Pathophysiology · 2022Review
- The lupus susceptibility allele DRB1*03:01 encodes a disease-driving epitope.Communications biology · 2022Article
- Endoplasmic Reticulum Stress, Oxidative Stress, and Rheumatic Diseases.Antioxidants (Basel, Switzerland) · 2022Review
- Increased susceptibility to organic dust exposure-induced inflammatory lung disease with enhanced rheumatoid arthritis-associated autoantigen expression in HLA-DR4 transgenic mice.Respiratory research · 2022Article
- HLA-G and the MHC Cusp Theory.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Associations between particular human leukocyte antigen (HLA) alleles and susceptibility to-or protection from-autoimmune diseases have been long observed. Allele-specific antigen presentation (AP) has been widely proposed as a culprit, but it is unclear whether HLA molecules might also have non-AP, disease-modulating effects. Here we demonstrate differential macrophage activation by HLA-DRB1 alleles known to associate with autoimmune disease risk or protection with resultant polarization of pro-inflammatory ("M1") versus anti-inflammatory ("M2") macrophages, respectively. RNA-sequencing analyses of in vitro-polarized macrophages in the presence of AP-incompetent short synthetic peptides corresponding to the third allelic hypervariable regions coded by those two HLA-DRB1 alleles showed reciprocal activation of pro- versus anti-inflammatory transcriptomes, with implication of corresponding gene ontologies and upstream regulators. These results identify a previously unrecognized mechanism of differential immune modulation by short HLA-DRB1-coded allelic epitopes independent of AP, and could shed new light on the mechanistic basis of HLA-disease association.
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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.