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Las células B activadoras de la respuesta innata agravan la aterosclerosis al estimular la inmunidad adaptativa del

Ingo Hilgendorf¹, Igor Theurl, Louisa M S Gerhardt

¹Center for Systems Biology, Massachusetts General Hospital, Boston (I.H., I.T., L.M.S.G., C.S.R., G.F.W., Y.I., C.W., H.Y.L., M.N., R.W., F.K.S.); Department of Internal Medicine VI, Infectious Diseases, Immunology Rheumatology, Pneumology, University Hospital of Innsbruck, Innsbruck, Austria (I.T.); Toronto General Research Institute, University Health Network, Toronto, ON, Canada (C.S.R., N.D.); Department of Medicine, University of California, San Diego, La Jolla (A.G., J.L.W.); Department of Gastroenterology, Hepatology and Infectious Diseases, University of Duesseldorf, Duesseldorf, Germany (T.A.W.H.); Department of Cardiology and Angiology I, University Heart Center Freiburg, Freiburg, Germany (C.W., A.Z.); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (G.K.S., P.L.); Department of Pathology (J.B.) and Division of Vascular Surgery (B.B.R.), Peter Munk Cardiac Centre, Toronto General Hospital, Toronto, ON, Canada; and Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.).

|February 4, 2014

Resumen

Las células B del activador de respuesta innata (IRA) promueven la aterosclerosis impulsando las respuestas de las células T auxiliares-1. Estas células B, que producen el factor estimulante de la colonia de macrófagos de granulocitos, empeoran la progresión de la enfermedad en ratones y humanos.

Área de la Ciencia:

Inmunología Inmunología.
Investigación Cardiovascular Investigación Cardiovascular Investigación Cardiovascular Investigación Cardiovascular Investigación Cardiovascular
Biología celular Biología celular.

Sus antecedentes:

La aterosclerosis implica la acumulación de leucocitos y lipoproteínas oxidadas.
Los mediadores derivados de leucocitos modulan el desarrollo de la lesión aterosclerótica.
Las células B del activador de respuesta innata (IRA) son un nuevo tipo de célula con funciones desconocidas en la aterosclerosis.

Objetivo del estudio:

Para investigar la función de las células IRA B en la aterosclerosis.
Determinar los mecanismos por los cuales las células IRA B influyen en las respuestas inmunes en la aterosclerosis.

Principales métodos:

Análisis de las poblaciones de células IRA B en modelos de aterosclerosis en ratones y humanos.
Uso de ratones quiméricos mixtos carentes de factor estimulante de colonias de macrófagos de granulocitos derivados de células B.
Evaluación de las poblaciones de células inmunes, expansión de células dendríticas y diferenciación de células T auxiliares.

Principales resultados:

Las células IRA B aumentan en los órganos linfoides secundarios durante la aterosclerosis a través de la señalización dependiente de Myd88.
Los ratones que carecen de factor estimulante de colonias de macrófagos de granulocitos derivados de células B muestran lesiones más pequeñas con macrófagos reducidos y células T efectoras.
Las células IRA B promueven la expansión de las células dendríticas clásicas, lo que lleva a la generación de células T auxiliares-1 y un interruptor IgG1-IgG2c.

Conclusiones:

Las células IRA B que producen el factor estimulante de las colonias de macrófagos de granulocitos exacerban la aterosclerosis.
Las células IRA B promueven un entorno inmune asociado al T-helper-1, empeorando las respuestas de los leucocitos en la aterosclerosis.

Palabras clave:

Los linfocitos B-linfocitos B-linfocitos B-linfocitos B-linfocitos Los linfocitos T-linfocitos también son linfocitos T.La aterosclerosis es la aterosclerosis.las células dendríticas.El factor estimulante de las colonias de granulocitos y macrófagos.Inmunología inmunología.

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