Antibody-mediated targeting of cleavage-specific OPN-T cell interactions.
T cells are crucial players in obesity-mediated adipose tissue inflammation. We hypothesized that osteopontin (OPN), an inflammatory protein with enhanced activity when proteolytically cleaved, affects the number of viable T cells in adipose tissue and assessed inhibition of the interaction between...
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doaj-ab0a37a4536d4796b1998b8bb7a7db632021-03-03T20:45:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01144e021493810.1371/journal.pone.0214938Antibody-mediated targeting of cleavage-specific OPN-T cell interactions.Bettina WankoMatteo TardelliAlexander JüretsAngelika NeuhoferGerhard PragerJohn MorserLawrence L LeungGünther StafflerMaximilian ZeydaThomas M StulnigT cells are crucial players in obesity-mediated adipose tissue inflammation. We hypothesized that osteopontin (OPN), an inflammatory protein with enhanced activity when proteolytically cleaved, affects the number of viable T cells in adipose tissue and assessed inhibition of the interaction between T cells and thrombin and matrix metalloproteinases-cleaved OPN using antibodies and postimmune sera. Gene expression of T cell markers in adipose tissue from wild-type (wt) and Spp1-/- (OPN deficient) mice was analyzed after 16 weeks of high fat diet (HFD) or low fat diet (LFD) feeding. CD3, CD8 and OPN gene expression in omental adipose tissue from individuals with obesity was measured. OPN-T cell interactions were assessed with a fluorescence-based adhesion assay and blocked with antibodies targeting OPN. Comparison of T cell gene expression in adipose tissue from wt and Spp1-/- mice showed that OPN affected the number of T cells while in humans, levels of OPN correlated with T cell markers in omental adipose tissue. The interaction between T cells and cleaved OPN was blocked by postimmune sera following OPN peptide vaccinations and with monoclonal antibodies. In conclusion, levels of OPN affected the number of T cells in obesity and antibodies against cleaved OPN antagonize OPN-T cell interactions.https://doi.org/10.1371/journal.pone.0214938 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bettina Wanko Matteo Tardelli Alexander Jürets Angelika Neuhofer Gerhard Prager John Morser Lawrence L Leung Günther Staffler Maximilian Zeyda Thomas M Stulnig |
spellingShingle |
Bettina Wanko Matteo Tardelli Alexander Jürets Angelika Neuhofer Gerhard Prager John Morser Lawrence L Leung Günther Staffler Maximilian Zeyda Thomas M Stulnig Antibody-mediated targeting of cleavage-specific OPN-T cell interactions. PLoS ONE |
author_facet |
Bettina Wanko Matteo Tardelli Alexander Jürets Angelika Neuhofer Gerhard Prager John Morser Lawrence L Leung Günther Staffler Maximilian Zeyda Thomas M Stulnig |
author_sort |
Bettina Wanko |
title |
Antibody-mediated targeting of cleavage-specific OPN-T cell interactions. |
title_short |
Antibody-mediated targeting of cleavage-specific OPN-T cell interactions. |
title_full |
Antibody-mediated targeting of cleavage-specific OPN-T cell interactions. |
title_fullStr |
Antibody-mediated targeting of cleavage-specific OPN-T cell interactions. |
title_full_unstemmed |
Antibody-mediated targeting of cleavage-specific OPN-T cell interactions. |
title_sort |
antibody-mediated targeting of cleavage-specific opn-t cell interactions. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2019-01-01 |
description |
T cells are crucial players in obesity-mediated adipose tissue inflammation. We hypothesized that osteopontin (OPN), an inflammatory protein with enhanced activity when proteolytically cleaved, affects the number of viable T cells in adipose tissue and assessed inhibition of the interaction between T cells and thrombin and matrix metalloproteinases-cleaved OPN using antibodies and postimmune sera. Gene expression of T cell markers in adipose tissue from wild-type (wt) and Spp1-/- (OPN deficient) mice was analyzed after 16 weeks of high fat diet (HFD) or low fat diet (LFD) feeding. CD3, CD8 and OPN gene expression in omental adipose tissue from individuals with obesity was measured. OPN-T cell interactions were assessed with a fluorescence-based adhesion assay and blocked with antibodies targeting OPN. Comparison of T cell gene expression in adipose tissue from wt and Spp1-/- mice showed that OPN affected the number of T cells while in humans, levels of OPN correlated with T cell markers in omental adipose tissue. The interaction between T cells and cleaved OPN was blocked by postimmune sera following OPN peptide vaccinations and with monoclonal antibodies. In conclusion, levels of OPN affected the number of T cells in obesity and antibodies against cleaved OPN antagonize OPN-T cell interactions. |
url |
https://doi.org/10.1371/journal.pone.0214938 |
work_keys_str_mv |
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