← Map/THREAD · M1-MACROPHAGE
Macrophage M1 Polarisation
The immune cells stuck in inflammatory mode. Where most AS treatments aim, indirectly.
Why this is a thread
Macrophages are immune cells that exist in two main states: M1 (inflammatory, the attack mode) and M2 (anti-inflammatory, the repair mode). In AS, too many macrophages are stuck in M1. Most existing AS treatments don't act on the macrophages themselves; they block the inflammatory signals (cytokines) that M1 macrophages produce. The papers in this thread are about the macrophages directly, what makes them go inflammatory, and the emerging idea that switching them back toward M2 could be a more direct way to treat the disease.
9 papers on the board
HLA-B27-associated gut microbiota and amino acid perturbations promote ankylosing spondylitis through M1 macrophage activation
Gut Microbes
Shows that HLA-B27, the gene most strongly linked to AS, reshapes which bacteria live in the gut and how the body handles certain amino acids, which in turn activates the inflammatory immune cells driving the disease. Suggests targeting the gut and these metabolic changes could become a real treatment route.
Breaking boundaries in ankylosing spondylitis: how innovative cell therapies reshape immunity
Frontiers in Immunology
Reviews mesenchymal stem cell and CAR-T cell therapy approaches for AS. MSC therapy shifts inflammatory M1 macrophages toward anti-inflammatory M2; CAR-T is still experimental for AS specifically. Current treatments fail to improve long-term prognosis, cell therapy is positioned as the next frontier.
The role of ETS2 in macrophage inflammation
DNA and Cell Biology
Direct follow-up to the 2024 Nature paper. Shows that ETS2 turns on several inflammatory signals at once, TNF, IL-23, IL-1β, and TL1A, the same signals current biologic drugs target one at a time.
The Role of IL-23 in the Development of Inflammatory Diseases
Biology (MDPI)
Maps the IL-23/Th17/IL-17 axis across psoriasis, rheumatoid arthritis, IBD, and multiple sclerosis. Confirms IL-23 as a key cross-disease therapeutic target, and reviews the current and emerging biologics that aim at it.
Gut microbiome and immune system crosstalk in chronic inflammatory diseases
Microorganisms
Review covering rheumatoid arthritis, IBD, psoriasis, lupus, asthma, and vasculitis, all sharing gut-immune disruption as a common mechanism. Synthesises FMT, dietary modification, and probiotic/prebiotic approaches.
Macrophage polarization: molecular mechanisms, disease implications, and targeted therapeutic strategies
Frontiers in Immunology
Reviews macrophage polarisation, the molecular mechanisms behind it, and emerging therapeutic strategies. Persistent M1 polarisation as the common driver of chronic disease, with JAK/STAT inhibition as a candidate way to restore the M1→M2 transition.
Macrophages: subtypes, distribution, polarization, immunomodulatory functions, and therapeutics
MedComm
Comprehensive review of macrophage subtypes, distribution, polarisation states, and therapeutic targeting. NF-κB and p38 MAPK pathway hijacking drives the maladaptive M1 shift, with links to DNA damage and senescence-associated secretory phenotype accumulation.
Therapeutic potential of CAR-expressing mesenchymal stem cells in inflammatory and autoimmune diseases
International Journal of Molecular Sciences
CAR-engineered mesenchymal stem cells combine the inflammation-homing properties of MSCs with antigen-specific targeting from CAR-T technology. Preclinical efficacy across multiple disease models, scalability and manufacturing remain the barriers to clinical adoption.
A disease-associated gene desert directs macrophage inflammation through ETS2
Nature
Identified a single 'switch' gene called ETS2, sitting on chromosome 21, that turns immune cells inflammatory across AS, IBD, and several other related diseases. Because no current drug targets ETS2, this points to a treatment direction beyond what's already available with TNF and IL-17 blockers.