Ferric Ammonium Citrate Upregulates PD-L1 Expression through Generation of Reactive Oxygen Species
Iron plays an important role in macrophage polarization by altering metabolic and redox status. However, the impact of iron on the immune status of macrophages is still controversial. In this study, we report that ferric ammonium citrate (FAC) upregulates PD-L1 expression in macrophages. FAC not onl...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2022/6284124 |
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| author | Eun Jung Choi Chang Hyun Jeon In-Kyu Lee |
| author_facet | Eun Jung Choi Chang Hyun Jeon In-Kyu Lee |
| author_sort | Eun Jung Choi |
| collection | DOAJ |
| description | Iron plays an important role in macrophage polarization by altering metabolic and redox status. However, the impact of iron on the immune status of macrophages is still controversial. In this study, we report that ferric ammonium citrate (FAC) upregulates PD-L1 expression in macrophages. FAC not only altered the phenotype of macrophages but also led to enriching immune-modulatory T cell subsets. Since iron is known to be a constituent of coenzymes facilitating metabolic processes in mitochondria, we examined the metabolic status of FAC-overloaded macrophages by measuring the oxygen consumption rate (OCR) and the represented coenzyme, aconitase. In addition to enhancement of metabolic processes, FAC accelerated the Fenton reaction in macrophages, which also contributed to the facilitation of oxygen consumption. We reasoned that the enhancement of the OCR leads to the production of reactive oxygen species (ROS), which are directly linked to PD-L1 induction. Using ferrostatin, rotenone, and N-acetyl-L-cysteine, we confirmed that metabolic and redox regulation is responsible for FAC-mediated PD-L1 expression. Furthermore, we suggested that FAC-induced ROS production may explain FAC-mediated pro- and anti-inflammatory responses in macrophages. These findings may extend our understanding of regulating iron concentration during immune checkpoint therapy in cancer patients. |
| format | Article |
| id | doaj-art-e64f40da817941579d0cb839f6055e4e |
| institution | OA Journals |
| issn | 2314-7156 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-e64f40da817941579d0cb839f6055e4e2025-08-20T02:21:03ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/6284124Ferric Ammonium Citrate Upregulates PD-L1 Expression through Generation of Reactive Oxygen SpeciesEun Jung Choi0Chang Hyun Jeon1In-Kyu Lee2Research Institute of Aging and MetabolismDepartment of Biomedical ScienceResearch Institute of Aging and MetabolismIron plays an important role in macrophage polarization by altering metabolic and redox status. However, the impact of iron on the immune status of macrophages is still controversial. In this study, we report that ferric ammonium citrate (FAC) upregulates PD-L1 expression in macrophages. FAC not only altered the phenotype of macrophages but also led to enriching immune-modulatory T cell subsets. Since iron is known to be a constituent of coenzymes facilitating metabolic processes in mitochondria, we examined the metabolic status of FAC-overloaded macrophages by measuring the oxygen consumption rate (OCR) and the represented coenzyme, aconitase. In addition to enhancement of metabolic processes, FAC accelerated the Fenton reaction in macrophages, which also contributed to the facilitation of oxygen consumption. We reasoned that the enhancement of the OCR leads to the production of reactive oxygen species (ROS), which are directly linked to PD-L1 induction. Using ferrostatin, rotenone, and N-acetyl-L-cysteine, we confirmed that metabolic and redox regulation is responsible for FAC-mediated PD-L1 expression. Furthermore, we suggested that FAC-induced ROS production may explain FAC-mediated pro- and anti-inflammatory responses in macrophages. These findings may extend our understanding of regulating iron concentration during immune checkpoint therapy in cancer patients.http://dx.doi.org/10.1155/2022/6284124 |
| spellingShingle | Eun Jung Choi Chang Hyun Jeon In-Kyu Lee Ferric Ammonium Citrate Upregulates PD-L1 Expression through Generation of Reactive Oxygen Species Journal of Immunology Research |
| title | Ferric Ammonium Citrate Upregulates PD-L1 Expression through Generation of Reactive Oxygen Species |
| title_full | Ferric Ammonium Citrate Upregulates PD-L1 Expression through Generation of Reactive Oxygen Species |
| title_fullStr | Ferric Ammonium Citrate Upregulates PD-L1 Expression through Generation of Reactive Oxygen Species |
| title_full_unstemmed | Ferric Ammonium Citrate Upregulates PD-L1 Expression through Generation of Reactive Oxygen Species |
| title_short | Ferric Ammonium Citrate Upregulates PD-L1 Expression through Generation of Reactive Oxygen Species |
| title_sort | ferric ammonium citrate upregulates pd l1 expression through generation of reactive oxygen species |
| url | http://dx.doi.org/10.1155/2022/6284124 |
| work_keys_str_mv | AT eunjungchoi ferricammoniumcitrateupregulatespdl1expressionthroughgenerationofreactiveoxygenspecies AT changhyunjeon ferricammoniumcitrateupregulatespdl1expressionthroughgenerationofreactiveoxygenspecies AT inkyulee ferricammoniumcitrateupregulatespdl1expressionthroughgenerationofreactiveoxygenspecies |