Identification and characterization of the recently evolved littoral cell as the chief source of SIRPα in human spleen (169.1)

Abstract

Abstract Asplenic individuals are compromised not only in their ability to destroy infectious agents, but are at increased risk of death from autoimmune disease, certain tumors, and ischemic heart disease. Enhanced mortality is attributed to lack of phagocytes sequestered in spleen that efficiently engulf and destroy appropriate targets, though related cells are found elsewhere in man. To investigate whether a unique population(s) regulates RBC and pathogen clearance and possibly filtration of altered self, we focused on a little-characterized cell that dominates the splenic red pulp of man and closely related primates, the venous sinus lining or littoral cell (LC). High expression of the formin FHOD1 outlines the LC population. Though endothelial-like in distribution LCs express several macrophage-associated proteins, the RBC antigen DARC and T-cell co-receptor CD8α/β though they lack lineage markers CD34 and CD45. Strikingly, SIRPα (CD172a) expression in human spleen concentrates on the LC, consistent with a key role in RBC turnover and elimination versus release of infected or altered self. Human LCs (SIRPα+, FHOD1+, CD8α+, CD34-, CD45-) comprise a highly specialized barrier cell population that emerged late in the course of evolution upon CD8 expression. Unique to higher primates (Hominidae), LCs may provide the ultimate filtration function(s) of human spleen.