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Neutrophils as Drivers of Immune Dysregulation in Autoimmune Diseases with Skin Manifestations

  • Author Footnotes
    3 These authors contributed equally to this work.
    Shuichiro Nakabo
    Footnotes
    3 These authors contributed equally to this work.
    Affiliations
    Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
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  • Author Footnotes
    3 These authors contributed equally to this work.
    Jorge Romo-Tena
    Footnotes
    3 These authors contributed equally to this work.
    Affiliations
    Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA

    Medical Science PhD Program, School of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
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  • Mariana J. Kaplan
    Correspondence
    Correspondence: Mariana J. Kaplan, Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 10 Center Drive, 12N248C, Bethesda, Maryland 20892–1930, USA.
    Affiliations
    Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
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  • Author Footnotes
    3 These authors contributed equally to this work.
      Dysregulation in the phenotype and function of neutrophils may play important roles in the initiation and perpetuation of autoimmune responses, including conditions affecting the skin. Neutrophils can have local and systemic effects on innate and adaptive immune cells as well as on resident cells in the skin, including keratinocytes (KCs). Aberrant formation/clearance of neutrophil extracellular traps (NETs) in systemic autoimmunity and chronic inflammatory diseases have been associated with the externalization of modified autoantigens in peripheral blood and tissues. NETs can impact the function of many cells, including macrophages, lymphocytes, dendritic cells, fibroblasts, and KCs. Emerging evidence has unveiled the pathogenic key roles of neutrophils in systemic lupus erythematosus, idiopathic inflammatory myopathies, psoriasis, hidradenitis suppurativa, and other chronic inflammatory conditions. As such, neutrophil-targeting strategies represent promising therapeutic options for these diseases.

      Abbreviations:

      BSLE (bullous systemic lupus erythematosus), DC (dendritic cell), DM (dermatomyositis), GPP (generalized pustular psoriasis), HS (hidradenitis suppurativa), IC (immune complex), IIM (idiopathic inflammatory myopathy), IL-36R (IL-36 receptor), KC (keratinocyte), LDG (low-density granulocyte), mROS (mitochondrial ROS), NET (neutrophil extracellular trap), NLR (neutrophil-to-lymphocyte ratio), PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne), pDC (plasmacytoid dendritic cell), PG (pyoderma gangrenosum), rTEM (reverse transmigration), SLE (systemic lupus erythematosus), Th (T helper), TLR (toll-like receptor)
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