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Metformin Suppresses MHC-Restricted Antigen Presentation by Inhibiting Co-Stimulatory Factors and MHC Molecules in APCs

Metformin is widely used for T2D therapy but its cellular mechanism of action is undefined. Recent studies on the mechanism of metformin in T2D have demonstrated involvement of the immune system. Current immunotherapies focus on the potential of immunomodulatory strategies for the treatment of T2D....

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Autores principales: Shin, Seulmee, Hyun, Bobae, Lee, Aeri, Kong, Hyunseok, Han, Shinha, Lee, Chong-Kil, Ha, Nam-Joo, Kim, Kyungjae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society of Applied Pharmacology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3762296/
https://www.ncbi.nlm.nih.gov/pubmed/24009856
http://dx.doi.org/10.4062/biomolther.2012.094
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author Shin, Seulmee
Hyun, Bobae
Lee, Aeri
Kong, Hyunseok
Han, Shinha
Lee, Chong-Kil
Ha, Nam-Joo
Kim, Kyungjae
author_facet Shin, Seulmee
Hyun, Bobae
Lee, Aeri
Kong, Hyunseok
Han, Shinha
Lee, Chong-Kil
Ha, Nam-Joo
Kim, Kyungjae
author_sort Shin, Seulmee
collection PubMed
description Metformin is widely used for T2D therapy but its cellular mechanism of action is undefined. Recent studies on the mechanism of metformin in T2D have demonstrated involvement of the immune system. Current immunotherapies focus on the potential of immunomodulatory strategies for the treatment of T2D. In this study, we examined the effects of metformin on the antigen-presenting function of antigen-presenting cells (APCs). Metformin decreased both MHC class I and class II-restricted presentation of OVA and suppressed the expression of both MHC molecules and co-stimulatory factors such as CD54, CD80, and CD86 in DCs, but did not affect the phagocytic activity toward exogenous OVA. The class II-restricted OVA presentation-regulating activity of metformin was also confirmed using mice that had been injected with metformin followed by soluble OVA. These results provide an understanding of the mechanisms of the T cell response-regulating activity of metformin through the inhibition of MHC-restricted antigen presentation in relation to its actions on APCs.
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spelling pubmed-37622962013-09-05 Metformin Suppresses MHC-Restricted Antigen Presentation by Inhibiting Co-Stimulatory Factors and MHC Molecules in APCs Shin, Seulmee Hyun, Bobae Lee, Aeri Kong, Hyunseok Han, Shinha Lee, Chong-Kil Ha, Nam-Joo Kim, Kyungjae Biomol Ther (Seoul) Articles Metformin is widely used for T2D therapy but its cellular mechanism of action is undefined. Recent studies on the mechanism of metformin in T2D have demonstrated involvement of the immune system. Current immunotherapies focus on the potential of immunomodulatory strategies for the treatment of T2D. In this study, we examined the effects of metformin on the antigen-presenting function of antigen-presenting cells (APCs). Metformin decreased both MHC class I and class II-restricted presentation of OVA and suppressed the expression of both MHC molecules and co-stimulatory factors such as CD54, CD80, and CD86 in DCs, but did not affect the phagocytic activity toward exogenous OVA. The class II-restricted OVA presentation-regulating activity of metformin was also confirmed using mice that had been injected with metformin followed by soluble OVA. These results provide an understanding of the mechanisms of the T cell response-regulating activity of metformin through the inhibition of MHC-restricted antigen presentation in relation to its actions on APCs. The Korean Society of Applied Pharmacology 2013-01 /pmc/articles/PMC3762296/ /pubmed/24009856 http://dx.doi.org/10.4062/biomolther.2012.094 Text en Copyright ©2013, The Korean Society of Applied Pharmacology http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Shin, Seulmee
Hyun, Bobae
Lee, Aeri
Kong, Hyunseok
Han, Shinha
Lee, Chong-Kil
Ha, Nam-Joo
Kim, Kyungjae
Metformin Suppresses MHC-Restricted Antigen Presentation by Inhibiting Co-Stimulatory Factors and MHC Molecules in APCs
title Metformin Suppresses MHC-Restricted Antigen Presentation by Inhibiting Co-Stimulatory Factors and MHC Molecules in APCs
title_full Metformin Suppresses MHC-Restricted Antigen Presentation by Inhibiting Co-Stimulatory Factors and MHC Molecules in APCs
title_fullStr Metformin Suppresses MHC-Restricted Antigen Presentation by Inhibiting Co-Stimulatory Factors and MHC Molecules in APCs
title_full_unstemmed Metformin Suppresses MHC-Restricted Antigen Presentation by Inhibiting Co-Stimulatory Factors and MHC Molecules in APCs
title_short Metformin Suppresses MHC-Restricted Antigen Presentation by Inhibiting Co-Stimulatory Factors and MHC Molecules in APCs
title_sort metformin suppresses mhc-restricted antigen presentation by inhibiting co-stimulatory factors and mhc molecules in apcs
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3762296/
https://www.ncbi.nlm.nih.gov/pubmed/24009856
http://dx.doi.org/10.4062/biomolther.2012.094
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