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The sex-biased chromatin modifier SMC1A promotes autoimmunity by shaping inflammatory pathways in patients with SLE

Author

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  • Despoina Kosmara

    (Foundation for Research and Technology—Hellas (FORTH), Institute of Molecular Biology and Biotechnology (IMBB)
    University of Crete Medical School, Rheumatology and Clinical Immunology)

  • Sofia Papanikolaou

    (Foundation for Research and Technology—Hellas (FORTH), Institute of Molecular Biology and Biotechnology (IMBB)
    University of Crete Medical School, Rheumatology and Clinical Immunology
    Biomedical Sciences Research Center “Alexander Fleming”, Institute of Bioinnovation)

  • Chrysoula Stathopoulou

    (Foundation for Research and Technology—Hellas (FORTH), Institute of Molecular Biology and Biotechnology (IMBB)
    University of Crete Medical School, Rheumatology and Clinical Immunology)

  • Dionysios Papamatheakis

    (Foundation for Research and Technology—Hellas (FORTH), Institute of Molecular Biology and Biotechnology (IMBB)
    University of Crete, Heraklion, Department of Biology)

  • Giannis Vatsellas

    (Biomedical Research Foundation Academy of Athens, Greek Genome Center)

  • Arianna Cimmarrusti

    (Foundation for Research and Technology—Hellas (FORTH), Institute of Molecular Biology and Biotechnology (IMBB)
    University of Crete Medical School, Rheumatology and Clinical Immunology)

  • Aggelos Banos

    (Biomedical Research Foundation Academy of Athens, Center of Clinical, Experimental Surgery and Translational Research)

  • Prodromos Sidiropoulos

    (Foundation for Research and Technology—Hellas (FORTH), Institute of Molecular Biology and Biotechnology (IMBB)
    University of Crete Medical School, Rheumatology and Clinical Immunology)

  • Matthieu D. Lavigne

    (Foundation for Research and Technology—Hellas (FORTH), Institute of Molecular Biology and Biotechnology (IMBB))

  • Panayotis Verginis

    (Foundation for Research and Technology—Hellas (FORTH), Institute of Molecular Biology and Biotechnology (IMBB)
    University of Crete, Laboratory of Immune Regulation and Tolerance, Division of Basic Sciences, Medical School)

  • Dimitrios Boumpas

    (Biomedical Research Foundation Academy of Athens, Center of Clinical, Experimental Surgery and Translational Research)

  • Charalampos Spilianakis

    (Foundation for Research and Technology—Hellas (FORTH), Institute of Molecular Biology and Biotechnology (IMBB)
    University of Crete, Heraklion, Department of Biology)

  • Dimitris Konstantopoulos

    (Biomedical Sciences Research Center “Alexander Fleming”, Institute of Bioinnovation)

  • Christoforos Nikolaou

    (Biomedical Sciences Research Center “Alexander Fleming”, Institute of Bioinnovation)

  • George Bertsias

    (Foundation for Research and Technology—Hellas (FORTH), Institute of Molecular Biology and Biotechnology (IMBB)
    University of Crete Medical School, Rheumatology and Clinical Immunology)

Abstract

A strong female bias is characteristic of systemic lupus erythematosus (SLE), the prototypic systemic autoimmune disease. Here, through an unbiased transcriptome analysis, we report a pronounced female-biased expression of the cohesin complex subunit SMC1A, a genome architectural factor, in monocytes from SLE patients compared to those from healthy individuals or patients with ankylosing spondylitis, a non-sex-biased autoimmune disorder. Integration of SMC1A binding, chromatin activity, and accessibility in lupus-like monocytes reveals extensive SMC1A redistribution to active enhancers of immune/inflammatory genes, inducing their transcription. SLE monocyte transcriptomes demonstrate significant enrichment of female-biased immune/inflammatory genes among SMC1A targets, accompanied by increased secretion of cytokines including IL6, with enhanced SMC1A binding at their enhancers in lupus-like monocytes. Collectively, our study highlights SMC1A as a female-biased chromatin modifier that acquires a specific regulatory function during lupus, accentuating inflammatory pathways and providing mechanistic insights into the female-biased predisposition to SLE and other autoimmune diseases.

Suggested Citation

  • Despoina Kosmara & Sofia Papanikolaou & Chrysoula Stathopoulou & Dionysios Papamatheakis & Giannis Vatsellas & Arianna Cimmarrusti & Aggelos Banos & Prodromos Sidiropoulos & Matthieu D. Lavigne & Pana, 2025. "The sex-biased chromatin modifier SMC1A promotes autoimmunity by shaping inflammatory pathways in patients with SLE," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65309-7
    DOI: 10.1038/s41467-025-65309-7
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