公开(公告)号：US11680245B2

公开(公告)日：2023-06-20

申请号：US16463655

申请日：2017-11-30

申请人： INSTITUT PASTEUR ,  INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

发明人： James Di Santo ,  Ai Ing Lim

IPC分类号： G01N33/53 ,  C12N5/0789 ,  A61K49/00 ,  G01N33/50 ,  C12N5/0775 ,  G01N33/68 ,  G01N15/14

CPC分类号： C12N5/0647 ,  A61K49/0008 ,  C12N5/0662 ,  G01N15/14 ,  G01N33/5047 ,  G01N33/5094 ,  G01N33/6869 ,  C12N2501/2301 ,  C12N2501/2302 ,  C12N2501/2307

摘要： Innate lymphoid cells (ILCs) represent innate versions of T helper and cytotoxic T cells that differentiate from committed ILC precursors (ILCP). Still, how ILCP relate to mature tissue-resident ILCs remains unclear. ILCP that are present in the blood and all tested lymphoid and non-lymphoid human tissues were identified. Human ILCP fail to express the signature transcription factors (TF) and cytokine outputs of mature NK cells and ILCs but are epigenetically poised to do so. Human ILCP robustly generate all ILC subsets in vitro and in vivo. While human ILCP express RAR related orphan receptor C (RORC), circulating ILCP can be found in RORC-deficient patients that retain potential for EOMES+ NK cells, T-BET+ ILC1, GATA-3+ ILC2 and for IL-22+ but not for IL-17A+ ILC3. A model of tissue ILC differentiation (‘ILC-poiesis’) is proposed whereby diverse ILC subsets are generated in situ from ILCP in response to environmental stressors, inflammation and infection.

公开(公告)号：US09439404B2

公开(公告)日：2016-09-13

申请号：US14182773

申请日：2014-02-18

申请人： INSERM (Institut National de la Santé et de la Recherche Médicale) ,  INSTITUT PASTEUR

发明人： James Di Santo ,  Jean-Jacques Mention

IPC分类号： A01K67/027 ,  C12N15/85

CPC分类号： A01K67/0271 ,  A01K67/0275 ,  A01K2207/15 ,  A01K2217/075 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/02 ,  A01K2267/03 ,  C12N15/8509

摘要： The present invention relates to a transgenic animal model system based on the development of transgenic mice bearing components of the human immune system. Specifically, the invention relates to a Flk2 deficient Rag−/−γc−/− transgenic mouse and the engraftment of said mouse with human hematopoietic stem cells. The present invention further provides methods for increasing the numbers of functionally competent human dendritic cells and the hematopoietic targets cells that they interact with in said transgenic mouse through the administration of Flk2L. The transgenic animal model system of the invention may be used for testing human vaccine candidates, for screening potential immune adjuvants and for developing novel therapeutics.

摘要翻译： 本发明涉及一种基于携带人免疫系统成分的转基因小鼠的发育的转基因动物模型系统。 具体地，本发明涉及Flk2缺陷型Rag - / - γc - / - 转基因小鼠和所述小鼠与人类造血干细胞的移植。 本发明进一步提供了通过施用Flk2L来增加其在所述转基因小鼠中相互作用的功能胜任的人类树突状细胞和造血靶细胞的数量的方法。 本发明的转基因动物模型系统可用于测试人类候选疫苗，筛选潜在的免疫佐剂和开发新的治疗剂。