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 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.
Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, Immunology Department, C/Diego de León 62, 28006, Madrid, Spain.
Rafael
R
González-Tajuelo
Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, Immunology Department, C/Diego de León 62, 28006, Madrid, Spain.
Javier
J
Silván
Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, Immunology Department, C/Diego de León 62, 28006, Madrid, Spain.
Alicia
A
Pérez-Frías
Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, Immunology Department, C/Diego de León 62, 28006, Madrid, Spain.
María
M
de la Fuente-Fernández
FIB, IIS-Princesa, Hospital de laPrincesa, Cytometry and Autoimmunity Unit, C/Diego de León 62, 28006, Madrid, Spain.
Reyes
R
Tejedor
Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, Immunology Department, C/Diego de León 62, 28006, Madrid, Spain.
Marina
M
Espartero-Santos
FIB, IIS-Princesa, Hospital de la Princesa, Rheumatology Department, C/Diego de León 62, 28006, Madrid, Spain.|Biology Department, Facultad de Ciencias, Universidad Autónoma de Madrid and Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), C/Francisco Tomás y Valiente 7, 28049, Madrid, Spain.
Esther
E
Vicente-Rabaneda
Biology Department, Facultad de Ciencias, Universidad Autónoma de Madrid and Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), C/Francisco Tomás y Valiente 7, 28049, Madrid, Spain.
Ángeles
Á
Juarranz
FIB, IIS-Princesa, Hospital de laPrincesa, Cytometry and Autoimmunity Unit, C/Diego de León 62, 28006, Madrid, Spain.
Cecilia
C
Muñoz-Calleja
FIB, IIS-Princesa, Hospital de la Princesa, Rheumatology Department, C/Diego de León 62, 28006, Madrid, Spain.
Santos
S
Castañeda
Pathology Department, Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 4, 28029, Madrid, Spain.
Carlos
C
Gamallo
Fundación de Investigación Biomédica (FIB), Instituto de Investigación Sanitaria-Princesa (IIS-Princesa), Hospital de la Princesa, Immunology Department, C/Diego de León 62, 28006, Madrid, Spain.
Ana
A
Urzainqui
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D005260:Female; D018858:Germinal Center / Q000473:pathology; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008178:Lupus Erythematosus, Cutaneous / Q000235:genetics* / Q000276:immunology; D016131:Lymphocyte Subsets; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000235:genetics* / Q000378:metabolism; D012867:Skin / Q000098:blood supply / Q000378:metabolism; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D020381:Interleukin-17; D019007:P-Selectin; D016753:Interleukin-10