Brief report: Reduced expression of CD18 leads to the in vivo expansion of hematopoietic stem cells in mouse bone marrow

Abstract

Leukocyte adhesion deficiency type-I is a primary immunodeficiency caused by mutations in the ITGB2 gene (CD18 leukocyte integrin) which lead to defects in leukocyte extravasation. To investigate the role of CD18 in hematopoietic stem cell (HSC) biology, we have thoroughly characterized the HSCs of CD18 Itgb2tm1bay hypomorphic mice (CD18HYP) both by flow cytometry and using in vitro and in vivo transplantation assays. Flow cytometry analyses and cultures in methyl cellulose revealed that bone marrow (BM) from CD18HYP mice was enriched in hematopoietic precursors, mainly early quiescent short-term and long-term Hematopoietic progenitors cells. Strikingly, BM competition assays showed a progressive expansion of CD18HYP-derived hematopoiesis in recipient mice. Additionally, we provide evidence that this HSC expansion was not caused by an increased homing capacity of CD18HYP HSCs or by alterations in the hematopoietic environment of CD18HYP mice due to defects in neutrophils clearance. On the contrary, our data demonstrated that the reduced expression of CD18 causes a cell-autonomous expansion in the HSC compartment, thus revealing unexpected regulatory functions for CD18 in mouse HSCs.