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

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/*deficiency ; Hematopoietic Stem Cells/*physiology ; Immune Reconstitution/*physiology ; Lymphocytes/*immunology ; Neutrophils/*immunology; Animals ; Bone Marrow Transplantation ; Catalytic Domain/genetics ; Cell Differentiation/immunology ; Cell Proliferation ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/genetics ; Female ; Fetus ; Gene Knock-In Techniques ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/radiation effects ; Immune System/radiation effects ; Liver/cytology ; Loss of Function Mutation ; Lymphocytes/radiation effects ; Male ; Mice ; Mice, Transgenic ; Models, Animal ; Neutrophils/radiation effects ; Point Mutation ; Transplantation Chimera/immunology ; Whole-Body Irradiation

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 (DPP9 ^S729A ) 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 DPP9 ^S729A -reconstituted mice. In secondary chimeric mice, cells of DPP9 ^S729A -origin cells displayed enhanced engraftment compared to WT. However, we observed no differences in myeloid or lymphoid lineage reconstitution between WT and DPP9 ^S729A 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.

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EC 3.4.14.- (Dipeptidyl-Peptidases and Tripeptidyl-Peptidases)
EC 3.4.14.5 (dipeptidyl peptidase 9, mouse)

Date Created: 20190516 Date Completed: 20201029 Latest Revision: 20210109

20221213

PMC6513830

10.1038/s41598-019-43739-w

31086209