Lymphocytes are a major source of circulating soluble dipeptidyl peptidase 4

Summary Dipeptidyl peptidase 4 (DPP4, CD26) is a serine protease that is expressed constitutively by many haematopoietic and non‐haematopoietic tissues. It exists as a membrane‐associated protein, as well as in an active, soluble form (herein called sDPP4), present at high concentrations in bodily f...

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Published in:	Clinical and experimental immunology Vol. 194; no. 2; pp. 166 - 179
Main Authors:	Casrouge, A., Sauer, A.V., Barreira da Silva, R., Tejera‐Alhambra, M., Sánchez‐Ramón, S., ICAReB, Cancrini, C., Ingersoll, M.A., Aiuti, A., Albert, M.L.
Format:	Journal Article
Language:	English
Published:	England Oxford University Press 01-11-2018 Wiley John Wiley and Sons Inc
Subjects:	Animals Biomarkers Biomarkers - metabolism Bodily Secretions Body fluids Bone marrow CD8 antigen Cell activation chemokines Dipeptidyl Peptidase 4 - genetics Dipeptidyl Peptidase 4 - metabolism Dipeptidyl-peptidase IV Disease Models, Animal Hematopoiesis - genetics Humans Immune system Immunodeficiency immunodeficiency diseases Immunology Infectious diseases Influenza A virus - physiology Life Sciences Lymphocytes Lymphocytes T Lymphopenia Membrane proteins Membrane Proteins - metabolism Mice Mice, Inbred C57BL Mice, Knockout Original Orthomyxoviridae Infections - immunology Peptidase Population studies Serine Serine proteinase Severe Combined Immunodeficiency - immunology Solubility T cells T-Lymphocytes - immunology Transplantation Chimera T cells chemokines immunodeficiency diseases
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Summary:	Summary Dipeptidyl peptidase 4 (DPP4, CD26) is a serine protease that is expressed constitutively by many haematopoietic and non‐haematopoietic tissues. It exists as a membrane‐associated protein, as well as in an active, soluble form (herein called sDPP4), present at high concentrations in bodily fluids. Despite the proposed use of sDPP4 as a biomarker for multiple diseases, its cellular sources are not well defined. Here, we report that individuals with congenital lymphocyte immunodeficiency had markedly lower serum concentrations of sDPP4, which were restored upon successful treatment and restoration of lymphocyte haematopoiesis. Using irradiated lymphopenic mice and wild‐type to Dpp4–/– reciprocal bone marrow chimeric animals, we found that haematopoietic cells were a major source of circulating sDPP4. Furthermore, activation of human and mouse T lymphocytes resulted in increased sDPP4, providing a mechanistic link between immune system activation and sDPP4 concentration. Finally, we observed that acute viral infection induced a transient increase in sDPP4, which correlated with the expansion of antigen‐specific CD8+ T cell responses. Our study demonstrates that sDPP4 concentrations are determined by the frequency and activation state of lymphocyte populations. Insights from these studies will support the use of sDPP4 concentration as a biomarker for inflammatory and infectious diseases. Circulating sDPP4 is derived from lymphocytes. Dipeptidyl peptidase 4 (DPP4) is a serine protease that exists as a membrane‐associated protein as well as in an active, soluble form (referred to as sDPP4). This manuscript contributes to the identification of lymphocytes as a major cellular sources of sDPP4. In one experiment (outlined here), wildtype to Dpp4‐/‐ reciprocal bone marrow chimeric animals were used to demonstrate that hematopoietic cells reconstituted sDPP4 in knockout hosts.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-2 PMCID: PMC6194339
ISSN:	0009-9104 1365-2249
DOI:	10.1111/cei.13163