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Co-Culture of Murine Small Intestine Epithelial Organoids with Innate Lymphoid Cells
Published on: March 23, 2022
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Las células linfoides innatas del hígado tipo 1 se desarrollan localmente a través de un bucle dependiente de
Lu Bai1,2, Margaux Vienne3, Ling Tang1,2
1Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Science (New York, N.Y.)
|March 26, 2021
Resumen
Los hígados de ratones adultos contienen células madre que se convierten en células linfoides innatas del hígado tipo 1 (ILC1). El interferón-gamma (IFN-γ) crea un ciclo de retroalimentación, promoviendo el desarrollo de ILC1 dentro del hígado.
Área de la Ciencia:
- Inmunología
- La hematopoyesis
- Biología celular
Sus antecedentes:
- Las vías de desarrollo de los linfocitos residentes en el tejido, como las células linfoides innatas del hígado tipo 1 (ILC1), no se comprenden completamente.
- La composición de las células inmunes del hígado está influenciada por la hematopoyesis extramedular, pero los mecanismos específicos no están claros.
Objetivo del estudio:
- Para aclarar el origen y la regulación del desarrollo de las células linfoides innatas del hígado tipo 1 (ILC1) en ratones adultos.
- Investigar el papel del interferón gamma (IFN-γ) en el desarrollo in situ de las células ILC1 del hígado.
Principales métodos:
- Aislamiento y caracterización de células madre y progenitoras hematopoyéticas de hígado de ratón adulto.
- Citometría de flujo y clasificación celular para identificar poblaciones celulares específicas (Lin-Sca-1+Mac-1+, Lin-CD122+CD49a+).
- Ensayos in vitro e in vivo para evaluar la diferenciación de las células progenitoras y la regulación dependiente de las citocinas.
Principales resultados:
- Los hígados de ratones adultos albergan células madre hematopoyéticas Lin-Sca-1 + Mac-1 + derivadas del hígado fetal.
- Un subconjunto de estos progenitores (Lin-CD122+CD49a+) genera ILC1s hepáticos pero no las células asesinas naturales convencionales.
- El interferón-gamma (IFN-γ) producido por ILC1s maduros actúa sobre los progenitores de IFN-γR+ para promover un mayor desarrollo de ILC1 in situ, estableciendo un bucle dependiente de IFN-γ.
Conclusiones:
- La hematopoyesis extramedular en el hígado adulto contribuye al conjunto de progenitores hepáticos de ILC1.
- Un bucle de retroalimentación dependiente de IFN-γ autocrino / paracrino impulsa el desarrollo in situ y la expansión de las células ILC1 del hígado.
- Este estudio revela un nuevo mecanismo para la homeostasis de las células inmunes y la especialización inmune regional dentro del hígado.
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