{"id":49703,"date":"2024-06-05T09:18:18","date_gmt":"2024-06-05T16:18:18","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=49703"},"modified":"2024-06-05T10:14:47","modified_gmt":"2024-06-05T17:14:47","slug":"cooperative-proteins-help-the-immune-system-identify-and-attack-invaders","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/es\/news-release\/cooperative-proteins-help-the-immune-system-identify-and-attack-invaders\/","title":{"rendered":"Las prote\u00ednas cooperativas ayudan al sistema inmunitario a identificar y atacar a los invasores"},"content":{"rendered":"

LA JOLLA\u2014Bacterias, par\u00e1sitos, virus: el sistema inmunitario los combate a todos. En la primera l\u00ednea de la respuesta inmunitaria humana se encuentran unas c\u00e9lulas llamadas macr\u00f3fagos, que son responsables de identificar correctamente a los intrusos y luego dirigir c\u00f3mo responde todo el sistema inmunitario. Investigadores del Salk Institute han descubierto ahora un mecanismo molecular que ayuda a los macr\u00f3fagos a montar una respuesta coordinada adaptada a un desaf\u00edo inmunitario espec\u00edfico. \r\n<\/p>

\r\nLa activaci\u00f3n de los macr\u00f3fagos requiere el trabajo de tres versiones de un complejo proteico llamado SWI\/SNF: cBAF, ncBAF y PBAF. Los cient\u00edficos ya sab\u00edan que estas variantes ten\u00edan estructuras ligeramente diferentes, pero los nuevos hallazgos revelan que estas diferencias tienen consecuencias funcionales reales. Investigadores de Salk descubrieron que cada variante juega un papel distinto en el inicio de las respuestas de los macr\u00f3fagos a los intrusos y, en consecuencia, c\u00f3mo el sistema inmunol\u00f3gico regula la inflamaci\u00f3n.\r\n<\/p>

\"From<\/a>
De izquierda a derecha: Diana Hargreaves y Jingwen Liao.

Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.
Cr\u00e9dito: Instituto Salk<\/figcaption><\/figure>

\r\nAl del. \r\n<\/p>

\r\nLos hallazgos fueron publicados en Inmunidad<\/a><\/em> el 5 de junio de 2024.\r\n<\/p>

\r\n\u201cLos macr\u00f3fagos son nuestra primera l\u00ednea de defensa y los reclutadores de las c\u00e9lulas inmunitarias adaptativas, por lo que comprender c\u00f3mo funcionan es clave para entender nuestra respuesta inmunitaria\u201d, afirma Diana Hargreaves<\/a>, autor principal y profesor asociado en Salk. \u201cSi podemos descubrir c\u00f3mo los macr\u00f3fagos adaptan sus respuestas a una determinada se\u00f1al inmunol\u00f3gica, tendremos una mejor idea de c\u00f3mo podemos atacarlos terap\u00e9uticamente para crear comportamientos deseables en el sistema inmunol\u00f3gico\u201d.\u201d\r\n<\/p>

\r\nLos macr\u00f3fagos son los primeros en detectar a un intruso en el organismo, por lo que les corresponde identificar con precisi\u00f3n al intruso y coordinar la respuesta del resto del sistema inmunitario. Para garantizar que se active la respuesta adecuada, los macr\u00f3fagos necesitan una se\u00f1alizaci\u00f3n interna muy espec\u00edfica.\r\n<\/p>

\r\nCada macr\u00f3fago contiene un conjunto de instrucciones de formaci\u00f3n de identidad codificadas en hebras de ADN, que est\u00e1n enrolladas alrededor de complejos de prote\u00ednas llamados histonas y luego enrolladas en una estructura tridimensional llamada cromatina. Los cambios en las histonas y la cromatina impactan la identidad de una c\u00e9lula, ya que sus modificaciones pueden exponer o ocultar tramos de ADN responsables del comportamiento de la c\u00e9lula. \r\n<\/p>\r\n

\"Three<\/a>
Tres variantes del complejo de prote\u00ednas SWI\/SNF, cBAF, ncBAF y PBAF, se re\u00fanen alrededor de una fogata asando malvaviscos, con distintivos que simbolizan sus identidades diferentes pero cooperativas. Juntas, coordinan la actividad de los macr\u00f3fagos y controlan la inflamaci\u00f3n, representada por el fuego.

Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.
Cr\u00e9dito: Instituto Salk<\/figcaption><\/figure>

\r\nSe sab\u00eda que el complejo proteico SWI\/SNF realizaba dichos cambios, pero no estaba claro si cada una de las tres variantes lo hac\u00eda de una manera \u00fanica o si conduc\u00eda a un comportamiento distinto de los macr\u00f3fagos. Para aprender m\u00e1s sobre las variantes de SWI\/SNF, los investigadores observaron c\u00f3mo respond\u00edan los macr\u00f3fagos en ratones a la infecci\u00f3n bacteriana y prestaron especial atenci\u00f3n a las diferencias entre la actividad de cBAF, ncBAF y PBAF.\r\n<\/p>

\r\n\"Encontramos que las variantes de SWI\/SNF desempe\u00f1an un prop\u00f3sito \u00fanico e importante en la reorganizaci\u00f3n de la cromatina en todo el genoma y en la habilitaci\u00f3n de las respuestas inflamatorias del macr\u00f3fago\u201d, dice la primera autora Jingwen Liao, estudiante de posgrado en el laboratorio de Hargreaves. \u2019Este es un gran avance en nuestra comprensi\u00f3n de c\u00f3mo los sistemas inmunitarios responden con un nivel de especificidad tan alto\u201c.\u201d\r\n<\/p>

\r\nAl enfrentarse a una amenaza bacteriana, cada una de las tres variantes de SWI\/SNF regul\u00f3 porciones distintas del ADN de los macr\u00f3fagos, produciendo respuestas celulares distintas. cBAF remodel\u00f3 la cromatina para promover la inflamaci\u00f3n, mientras que ncBAF modific\u00f3 histonas para estimular una respuesta antiviral. PBAF tambi\u00e9n modific\u00f3 histonas, pero el resultado de esas modificaciones fue menos claro que con cBAF o ncBAF.\r\n<\/p>

\r\nLos tres actuaron de forma distintiva y cooperativa para coordinar una compleja respuesta inmunitaria que solicita al resto del sistema inmunol\u00f3gico para eliminar las amenazas del cuerpo de manera efectiva y eficiente.\r\n<\/p>

\r\n\u201cLa inflamaci\u00f3n cr\u00f3nica es una causa importante de mortalidad en muchas enfermedades \u2014dice Hargreaves\u2014. Cuando los pacientes sucumben a la COVID, por ejemplo, a menudo es un producto de la inflamaci\u00f3n. Esto\u201d\r\n<\/p>

\r\nEl equipo seguir\u00e1 estudiando los efectos de la modificaci\u00f3n de las histonas por parte del PBAF en futuras investigaciones. Dado que los inhibidores del cBAF y del ncBAF ya se encuentran en ensayos cl\u00ednicos para el tratamiento del c\u00e1ncer, Hargreaves se muestra optimista respecto a la posibilidad de convertir sus hallazgos en futuros medicamentos para la inflamaci\u00f3n cr\u00f3nica.\r\n<\/p>

\r\nOtros autores incluyen a Josephine Ho y Mannix Burns en Salk, as\u00ed como a Emily Dykhuizen en la Universidad de Purdue.\r\n<\/p>

\r\nEl trabajo fue financiado por los National Institutes of Health (NCI CCSG: P30 014195, AI151123, GM128943, R21 MH128678-01), Pew-Stewart Scholars for Cancer Research y la American Cancer Society.<\/p>","protected":false},"featured_media":49726,"template":"","faculty":[74],"disease-research":[122,456],"class_list":["post-49703","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-diana-hargreaves","disease-research-immune-system-biology","disease-research-inflammation"],"acf":[],"yoast_head":"\nCooperative proteins help the immune system identify and attack invaders - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/es\/news-release\/cooperative-proteins-help-the-immune-system-identify-and-attack-invaders\/\" \/>\n<meta property=\"og:locale\" content=\"es_MX\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Cooperative proteins help the immune system identify and attack invaders - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Bacteria, parasites, viruses\u2014the immune system tackles them all. 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