Immune regeneration in irradiated mice is not impaired by the absence of DPP9 enzymatic activity

Autor:	Hui Emma Zhang, Quintin Lee, Mark D. Gorrell, Christopher J. Jolly, Adam Cook, Ben Roediger, Margaret G. Gall, Geoffrey W. McCaughan
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	0301 basic medicine Male Myeloid Liver cytology Neutrophils medicine.medical_treatment lcsh:Medicine Hematopoietic stem cell transplantation Mice 0302 clinical medicine Immune Reconstitution Loss of Function Mutation Catalytic Domain Gene Knock-In Techniques Lymphocytes lcsh:Science Bone Marrow Transplantation Myelopoiesis Innate immunity Multidisciplinary Chemistry Lymphopoiesis Hematopoietic Stem Cell Transplantation Hematopoietic stem cell Cell Differentiation medicine.anatomical_structure Liver Models Animal Female Whole-Body Irradiation Antigen presentation Mice Transgenic Article 03 medical and health sciences Immune system Fetus medicine Animals Point Mutation Dipeptidyl-Peptidases and Tripeptidyl-Peptidases B cell Cell Proliferation Transplantation Chimera lcsh:R Hematopoietic Stem Cells Molecular biology 030104 developmental biology Immune System lcsh:Q Bone marrow 030217 neurology & neurosurgery
Zdroj:	Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019) Scientific Reports
ISSN:	2045-2322
DOI:	10.1038/s41598-019-43739-w
Popis:	The ubiquitous intracellular protease dipeptidyl peptidase 9 (DPP9) has roles in antigen presentation and B cell signaling. To investigate the importance of DPP9 in immune regeneration, primary and secondary chimeric mice were created in irradiated recipients using fetal liver cells and adult bone marrow cells, respectively, using wild-type (WT) and DPP9 gene-knockin (DPP9S729A) enzyme-inactive mice. Immune cell reconstitution was assessed at 6 and 16 weeks post-transplant. Primary chimeric mice successfully regenerated neutrophils, natural killer, T and B cells, irrespective of donor cell genotype. There were no significant differences in total myeloid cell or neutrophil numbers between DPP9-WT and DPP9S729A-reconstituted mice. In secondary chimeric mice, cells of DPP9S729A-origin cells displayed enhanced engraftment compared to WT. However, we observed no differences in myeloid or lymphoid lineage reconstitution between WT and DPP9S729A donors, indicating that hematopoietic stem cell (HSC) engraftment and self-renewal is not diminished by the absence of DPP9 enzymatic activity. This is the first report on transplantation of bone marrow cells that lack DPP9 enzymatic activity.
Databáze:	OpenAIRE
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