P-Selectin preserves immune tolerance in mice and is reduced in human cutaneous lupus

Mice deficient in P-Selectin presented altered immunity/tolerance balance. We have observed that the absence of P-Selectin promotes splenomegaly with reduced naïve T cell population, elevated activated/effector T cell subset, increased germinal center B and Tfh populations and high production of aut...

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Published inScientific reports Vol. 7; no. 1; p. 41841
Main Authors González-Tajuelo, Rafael, Silván, Javier, Pérez-Frías, Alicia, de la Fuente-Fernández, María, Tejedor, Reyes, Espartero-Santos, Marina, Vicente-Rabaneda, Esther, Juarranz, Ángeles, Muñoz-Calleja, Cecilia, Castañeda, Santos, Gamallo, Carlos, Urzainqui, Ana
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 02.02.2017
Subjects
Anti-DNA antibodies
Antibodies
Antigen-antibody complexes
Autoantibodies
Cutaneous Lupus Erythematosus
Immunological tolerance
Inflammatory diseases
Interleukin 1
Interleukin 10
Interleukin 17
Kidneys
Leukocytes
Lupus
Lymphocytes
Lymphocytes T
P-selectin
Rodents
Splenomegaly
Systemic lupus erythematosus
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Summary:Mice deficient in P-Selectin presented altered immunity/tolerance balance. We have observed that the absence of P-Selectin promotes splenomegaly with reduced naïve T cell population, elevated activated/effector T cell subset, increased germinal center B and Tfh populations and high production of autoreactive antibodies. Moreover, 1.5-3-month-old P-selectin KO mice showed reduced IL-10-producing leukocytes in blood and a slightly reduced Treg population in the skin. With aging and, coinciding with disease severity, there is an increase in the IL17 circulating and dermal T cell subpopulations and reduction of dermal Treg. As a consequence, P-Selectin deficient mice developed a progressive autoimmune syndrome showing skin alterations characteristic of lupus prone mice and elevated circulating autoantibodies, including anti-dsDNA. Similar to human SLE, disease pathogenesis was characterized by deposition of immune complexes in the dermoepidermal junction and renal glomeruli, and a complex pattern of autoantibodies. More important, skin biopsies of cutaneous lupus erythematosus patients did not show increased expression of P-Selectin, as described for other inflammatory diseases, and the number of vessels expressing P-Selectin was reduced.
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These authors contributed equally to this work.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep41841