title: 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 Itgb2(tm1bay) hypomorphic mice (CD18(HYP) ) 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 CD18(HYP) 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 CD18(HYP) -derived hematopoiesis in recipient mice. Additionally, we provide evidence that this HSC expansion was not caused by an increased homing capacity of CD18(HYP) HSCs or by alterations in the hematopoietic environment of CD18(HYP) 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.
authors.affiliation: Division of Hematopoietic Innovative Therapies, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER), Madrid, Sapin; Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), Madrid, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Leon-Rico
authors.forename: Montserrat
authors.initials: M
authors.lastname: Aldea
authors.forename: Rebeca
authors.initials: R
authors.lastname: Sanchez
authors.forename: José C
authors.initials: JC
authors.lastname: Segovia
authors.forename: Linnea A
authors.initials: LA
authors.lastname: Weiss
authors.forename: Andrés
authors.initials: A
authors.lastname: Hidalgo
authors.forename: Juan A
authors.initials: JA
authors.lastname: Bueren
authors.forename: Elena
authors.initials: E
authors.lastname: Almarza
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism*; D018821:CD18 Antigens / Q000378:metabolism*; D016922:Cellular Senescence; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D009504:Neutrophils / Q000166:cytology
chemical_list: D018821:CD18 Antigens
keywords: Cell adhesion molecules; Hematopoietic stem cells; Neutrophil; Stem cell-microenvironment