Ly49E separates liver ILC1s into embryo-derived and postnatal subsets with different functions.

Area of Science:

• Immunology
• Cell Biology

Background:

• Type 1 innate lymphoid cells (ILC1s) are key immune regulators in the liver.
• The cellular diversity within liver ILC1 populations remains incompletely understood.

Purpose of the Study:

• To investigate the heterogeneity of liver ILC1s.
• To identify distinct subpopulations within liver ILC1s and their developmental origins and functions.

Main Methods:

• Single-cell RNA sequencing
• Flow cytometry
• Genetic fate-mapping analysis

Main Results:

• Liver ILC1s were classified into Ly49E-positive (Ly49E+) and Ly49E-negative (Ly49E-) subsets with unique features.
• Ly49E+ ILC1s derived from embryonic progenitors, persisted postnatally, and provided protection against cytomegalovirus in neonates.
• Ly49E- ILC1s developed postnatally from bone marrow and extramedullary progenitors, accumulating with age and mediating adult immune memory responses.

Conclusions:

• Ly49E serves as a marker to distinguish two functionally distinct liver ILC1 subpopulations.
• These subpopulations possess different origins and are biased towards neonatal innate immunity or adult adaptive immune memory.