Development of an Autoimmune Syndrome Affecting the Skin and Internal Organs in P-Selectin Glycoprotein Ligand 1 Leukocyte Receptor–Deficient Mice

Authors

  • A. Pérez-Frías,

    1. Fundación de Investigación Biomédica, Instituto de Investigación Sanitaria-Princesa, and Hospital de la Princesa, Madrid, Spain
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    • Ms Pérez-Frías and Mr. González-Tajuelo contributed equally to this work.

  • R. González-Tajuelo,

    1. Fundación de Investigación Biomédica, Instituto de Investigación Sanitaria-Princesa, and Hospital de la Princesa, Madrid, Spain
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    • Ms Pérez-Frías and Mr. González-Tajuelo contributed equally to this work.

  • N. Núñez-Andrade,

    1. Fundación de Investigación Biomédica, Instituto de Investigación Sanitaria-Princesa, and Hospital de la Princesa, Madrid, Spain
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  • R. Tejedor,

    1. Fundación de Investigación Biomédica, Instituto de Investigación Sanitaria-Princesa, and Hospital de la Princesa, Madrid, Spain
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  • M. J. García-Blanco,

    1. Fundación de Investigación Biomédica, Instituto de Investigación Sanitaria-Princesa, and Hospital de la Princesa, Madrid, Spain
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  • E. Vicente-Rabaneda,

    1. Fundación de Investigación Biomédica, Instituto de Investigación Sanitaria-Princesa, and Hospital de la Princesa, Madrid, Spain
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  • S. Castañeda,

    1. Fundación de Investigación Biomédica, Instituto de Investigación Sanitaria-Princesa, and Hospital de la Princesa, Madrid, Spain
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  • C. Gamallo,

    1. Fundación de Investigación Biomédica, Instituto de Investigación Sanitaria-Princesa, and Hospital de la Princesa, Madrid, Spain
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  • J. Silván,

    1. Fundación de Investigación Biomédica, Instituto de Investigación Sanitaria-Princesa, and Hospital de la Princesa, Madrid, Spain
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  • A. Esteban-Villafruela,

    1. Fundación de Investigación Biomédica, Instituto de Investigación Sanitaria-Princesa, and Hospital de la Princesa, Madrid, Spain
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  • L. Cubero-Rueda,

    1. Fundación de Investigación Biomédica, Instituto de Investigación Sanitaria-Princesa, and Hospital de la Princesa, Madrid, Spain
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  • C. García-García,

    1. Fundación de Investigación Biomédica, Instituto de Investigación Sanitaria-Princesa, and Hospital de la Princesa, Madrid, Spain
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  • C. Muñoz-Calleja,

    1. Fundación de Investigación Biomédica, Instituto de Investigación Sanitaria-Princesa, and Hospital de la Princesa, Madrid, Spain
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  • A. García-Diez,

    1. Fundación de Investigación Biomédica, Instituto de Investigación Sanitaria-Princesa, and Hospital de la Princesa, Madrid, Spain
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  • A. Urzainqui

    Corresponding author
    1. Fundación de Investigación Biomédica, Instituto de Investigación Sanitaria-Princesa, and Hospital de la Princesa, Madrid, Spain
    • Fundación de Investigación Biomédica, Instituto de Investigación Sanitaria-Princesa, Hospital de la Princesa, Diego de León 62, 28006 Madrid, Spain. E-mail: ana.urzainqui@salud.madrid.org

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Abstract

Objective

To define and characterize the progression of the spontaneous autoimmune disease that develops in mice in the absence of the leukocyte adhesion receptor P-selectin glycoprotein ligand 1 (PSGL-1).

Methods

Skin-resident immune cells from PSGL-1–deficient mice and C57BL/6 control mice of different ages were isolated and analyzed by flow cytometry. Biochemical parameters were analyzed in mouse serum and urine, and the presence of serum autoantibodies was investigated. Skin and internal organs were extracted, and their structure was analyzed histologically.

Results

Skin-resident innate and adaptive immune cells from PSGL-1−/− mice had a proinflammatory phenotype with an imbalanced T effector cell:Treg cell ratio. Sera from PSGL-1−/− mice had circulating autoantibodies commonly detected in connective tissue–related human autoimmune diseases. Biochemical and histologic analysis of skin and internal organs revealed skin fibrosis and structural and functional abnormalities in the lungs and kidneys. Furthermore, PSGL-1−/− mice exhibited vascular alterations, showing loss of dermal vessels, small vessel medial layer remodeling in the lungs and kidneys, and ischemic processes in the kidney that promote renal infarcts.

Conclusion

Our study demonstrates that immune system overactivation due to PSGL-1 deficiency triggers an autoimmune syndrome with characteristics similar to systemic sclerosis, including skin fibrosis, vascular alterations, and systemic organ involvement. These results suggest that PSGL-1 expression contributes to the maintenance of the homeostasis of the immune system and could act as a barrier for autoimmunity in mice.

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