Lymphocytes are a major source of circulating soluble dipeptidyl peptidase 4

A Casrouge, A V Sauer, R Barreira da Silva, M Tejera-Alhambra, S Sánchez-Ramón, ICAReB, C Cancrini, M A Ingersoll, A Aiuti, M L Albert

Research output: Contribution to journalReview article

Abstract

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.

Original languageEnglish
Pages (from-to)166-179
Number of pages14
JournalClinical and Experimental Immunology
Volume194
Issue number2
DOIs
Publication statusPublished - Nov 2018

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Dipeptidyl Peptidase 4
Biomarkers
Lymphocytes
CD8 Antigens
T-Lymphocytes
Hematopoiesis
Serine Proteases
Virus Diseases
Lymphocyte Activation
Communicable Diseases
Immune System
Membrane Proteins
Bone Marrow
Serum
Population

Cite this

Casrouge, A., Sauer, A. V., Barreira da Silva, R., Tejera-Alhambra, M., Sánchez-Ramón, S., ICAReB, ... Albert, M. L. (2018). Lymphocytes are a major source of circulating soluble dipeptidyl peptidase 4. Clinical and Experimental Immunology, 194(2), 166-179. https://doi.org/10.1111/cei.13163

Lymphocytes are a major source of circulating soluble dipeptidyl peptidase 4. / 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.

In: Clinical and Experimental Immunology, Vol. 194, No. 2, 11.2018, p. 166-179.

Research output: Contribution to journalReview article

Casrouge, A, Sauer, AV, Barreira da Silva, R, Tejera-Alhambra, M, Sánchez-Ramón, S, ICAReB, , Cancrini, C, Ingersoll, MA, Aiuti, A & Albert, ML 2018, 'Lymphocytes are a major source of circulating soluble dipeptidyl peptidase 4', Clinical and Experimental Immunology, vol. 194, no. 2, pp. 166-179. https://doi.org/10.1111/cei.13163
Casrouge A, Sauer AV, Barreira da Silva R, Tejera-Alhambra M, Sánchez-Ramón S, ICAReB et al. Lymphocytes are a major source of circulating soluble dipeptidyl peptidase 4. Clinical and Experimental Immunology. 2018 Nov;194(2):166-179. https://doi.org/10.1111/cei.13163
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. / Lymphocytes are a major source of circulating soluble dipeptidyl peptidase 4. In: Clinical and Experimental Immunology. 2018 ; Vol. 194, No. 2. pp. 166-179.
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AU - Casrouge, A

AU - Sauer, A V

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AU - Sánchez-Ramón, S

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AU - Cancrini, C

AU - Ingersoll, M A

AU - Aiuti, A

AU - Albert, M L

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N2 - 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.

AB - 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.

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