US2023323304A1PendingUtilityA1

Human innate lymphoid cell precursors: identification, characterization, applications

Assignee: PASTEUR INSTITUTPriority: Nov 30, 2016Filed: May 9, 2023Published: Oct 12, 2023
Est. expiryNov 30, 2036(~10.3 yrs left)· nominal 20-yr term from priority
A61K 40/11A61K 40/44A61K 40/10A61K 2239/38A61K 2239/31A61K 2300/00A61K 2121/00C12N 5/0647C12N 5/0634A61K 49/0008C12N 5/0662G01N 15/14G01N 33/5047G01N 33/5094G01N 33/6869C12N 2501/2301C12N 2501/2302C12N 2501/2307C12N 2501/2323C12N 2501/2312C12N 2501/2318C12N 2501/2325C12N 2501/42C12N 2501/2333C12N 2502/1352A61P 31/00A61P 35/00A61P 37/00A61P 37/02
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Claims

Abstract

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.

Claims

exact text as granted — not AI-modified
1 - 15 . (canceled) 
     
     
         16 . A purified population of innate lymphoid cell precursors (ILCPs), wherein at least 75% of the cells in the population have the phenotype 
 CD127+CD117+CD3-CRTh2-CD7+CD94-NKp44-CD26+,   CD127+CD1 17+CD3-CRTh2-CD7+CD94-NKp44-CD62L+, or   CD127+CD117+CD3-CRTh2-CD7+CD94-NKp44-CD26+CD62L+.   
     
     
         17 . The purified population of ILCPs of  claim 16 , wherein at least 90% of the cells in the population have the phenotype
 CD127+CD117+CD3-CRTh2-CD7+CD94-NKp44-CD26+,   CD127+CD1 17+CD3-CRTh2-CD7+CD94-NKp44-CD62L+, or   CD127+CD117+CD3-CRTh2-CD7+CD94-NKp44-CD26+CD62L+.   
     
     
         18 . The purified population of ILCPs of  claim 16 , wherein at least 75% of the cells in the population have the phenotype CD127+CD117+CD3-CRTh2-CD7+CD94-NKp44-CD26+. 
     
     
         19 . The purified population of ILCPs of  claim 16 , wherein at least 75% of the cells in the population have the phenotype CD127+CD117+CD3-CRTh2-CD7+CD94-NKp44-CD62L+. 
     
     
         20 . The purified population of ILCPs of  claim 16 , wherein at least 75% of the cells in the population have the phenotype CD127+CD117+CD3-CRTh2-CD7+CD94-NKp44-CD26+CD62L+. 
     
     
         21 . The purified population of ILCPs of  claim 17 , wherein at least 90% of the cells in the population have the phenotype CD127+CD117+CD3-CRTh2-CD7+CD94-NKp44-CD26+. 
     
     
         22 . The purified population of ILCPs of  claim 17 , wherein at least 90% of the cells in the population have the phenotype CD127+CD117+CD3-CRTh2-CD7+CD94-NKp44-CD62L+. 
     
     
         23 . The purified population of ILCPs of  claim 17 , wherein at least 90% of the cells in the population have the phenotype CD127+CD117+CD3-CRTh2-CD7+CD94-NKp44-CD26+CD62L+. 
     
     
         24 . The purified population of ILCPs of  claim 21 , comprising at least 10 4  ILCPs cells. 
     
     
         25 . The purified population of ILCPs of  claim 22 , comprising at least 10 4  ILCPs cells. 
     
     
         26 . The purified population of ILCPs of  claim 23 , comprising at least 10 4  ILCPs cells. 
     
     
         27 . The purified population of ILCPs of  claim 21 , comprising at least 10 6  ILCPs cells. 
     
     
         28 . The purified population of ILCPs of  claim 22 , comprising at least 10 6  ILCPs cells. 
     
     
         29 . The purified population of ILCPs of  claim 23 , comprising at least 10 6  ILCPs cells. 
     
     
         30 . The purified population of ILCPs of  claim 24 , in a medium containing IL-2 and IL-1β. 
     
     
         31 . The purified population of ILCPs of  claim 25 , in a medium containing IL-2 and IL-1β. 
     
     
         32 . The purified population of ILCPs of  claim 26 , in a medium containing L-2 and IL-1β. 
     
     
         33 . The purified population of ILCPs of  claim 27 , in a medium containing IL-2 and IL-1β. 
     
     
         34 . The purified population of ILCPs of  claim 28 , in a medium containing IL-2 and IL-1β. 
     
     
         35 . The purified population of ILCPs of  claim 29 , in a medium containing IL-2 and IL-1β.

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