High iodine promotes autoimmune thyroid disease by activating hexokinase 3 and inducing polarization of macrophages towards M1
Autoimmune thyroid disease (AITD), the most common autoimmune disease, includes Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). Currently, the pathogenesis of AITD is not fully understood. Our study aimed to examine the presence of macrophage polarization imbalance in AITD patients, to invest...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1009932/full |
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| author | Tiantian Cai Peng Du Lixia Suo Xiaozhen Jiang Qiu Qin Ronghua Song Xiaorong Yang Yanfei Jiang Jin-an Zhang |
| author_facet | Tiantian Cai Peng Du Lixia Suo Xiaozhen Jiang Qiu Qin Ronghua Song Xiaorong Yang Yanfei Jiang Jin-an Zhang |
| author_sort | Tiantian Cai |
| collection | DOAJ |
| description | Autoimmune thyroid disease (AITD), the most common autoimmune disease, includes Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). Currently, the pathogenesis of AITD is not fully understood. Our study aimed to examine the presence of macrophage polarization imbalance in AITD patients, to investigate whether high iodine can cause macrophage polarization imbalance, and to investigate the role of key genes of metabolic reprogramming in macrophage polarization imbalance caused by high iodine. We synergistically used various research strategies such as systems biology, clinical studies, cell culture and mouse disease models. Gene set enrichment analysis (GSEA) revealed that M1 macrophage hyperpolarization was involved in the pathogenesis of AITD. In vitro and in vivo experiments showed that high iodine can affect the polarization of M1 or M2 macrophages and their related cytokines. Robust rank aggregation (RRA) method revealed that hexokinase 3 (HK3) was the most aberrantly expressed metabolic gene in autoimmune diseases. In vitro and in vivo studies revealed HK3 could mediate macrophage polarization induced by high iodine. In summary, hyperpolarization of M1-type macrophages is closely related to the pathogenesis of AITD. High iodine can increase HK3 expression in macrophages and promote macrophage polarization towards M1. Targeting HK3 can inhibit M1 polarization induced by high iodine. |
| first_indexed | 2024-04-11T19:37:44Z |
| format | Article |
| id | doaj.art-d10a5b7101c444799f5867c22d44880b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T19:37:44Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d10a5b7101c444799f5867c22d44880b2022-12-22T04:06:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.10099321009932High iodine promotes autoimmune thyroid disease by activating hexokinase 3 and inducing polarization of macrophages towards M1Tiantian Cai0Peng Du1Lixia Suo2Xiaozhen Jiang3Qiu Qin4Ronghua Song5Xiaorong Yang6Yanfei Jiang7Jin-an Zhang8Department of Endocrinology & Rheumatology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, ChinaDepartment of Endocrinology & Rheumatology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, ChinaDepartment of Endocrinology, Shanghai University of Medicine & Health Sciences Affiliated Jiading District Central Hospital, Shanghai, ChinaDepartment of Endocrinology, Shanghai Pudong New Area People’s Hospital, Shanghai, ChinaDepartment of Endocrinology & Rheumatology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, ChinaDepartment of Endocrinology & Rheumatology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, ChinaDepartment of Endocrinology & Rheumatology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, ChinaDepartment of Endocrinology & Rheumatology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, ChinaDepartment of Endocrinology & Rheumatology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, ChinaAutoimmune thyroid disease (AITD), the most common autoimmune disease, includes Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). Currently, the pathogenesis of AITD is not fully understood. Our study aimed to examine the presence of macrophage polarization imbalance in AITD patients, to investigate whether high iodine can cause macrophage polarization imbalance, and to investigate the role of key genes of metabolic reprogramming in macrophage polarization imbalance caused by high iodine. We synergistically used various research strategies such as systems biology, clinical studies, cell culture and mouse disease models. Gene set enrichment analysis (GSEA) revealed that M1 macrophage hyperpolarization was involved in the pathogenesis of AITD. In vitro and in vivo experiments showed that high iodine can affect the polarization of M1 or M2 macrophages and their related cytokines. Robust rank aggregation (RRA) method revealed that hexokinase 3 (HK3) was the most aberrantly expressed metabolic gene in autoimmune diseases. In vitro and in vivo studies revealed HK3 could mediate macrophage polarization induced by high iodine. In summary, hyperpolarization of M1-type macrophages is closely related to the pathogenesis of AITD. High iodine can increase HK3 expression in macrophages and promote macrophage polarization towards M1. Targeting HK3 can inhibit M1 polarization induced by high iodine.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1009932/fullautoimmune thyroid diseasegraves’ diseasehashimoto’s thyroiditismacrophage polarizationiodinehexokinase 3 |
| spellingShingle | Tiantian Cai Peng Du Lixia Suo Xiaozhen Jiang Qiu Qin Ronghua Song Xiaorong Yang Yanfei Jiang Jin-an Zhang High iodine promotes autoimmune thyroid disease by activating hexokinase 3 and inducing polarization of macrophages towards M1 Frontiers in Immunology autoimmune thyroid disease graves’ disease hashimoto’s thyroiditis macrophage polarization iodine hexokinase 3 |
| title | High iodine promotes autoimmune thyroid disease by activating hexokinase 3 and inducing polarization of macrophages towards M1 |
| title_full | High iodine promotes autoimmune thyroid disease by activating hexokinase 3 and inducing polarization of macrophages towards M1 |
| title_fullStr | High iodine promotes autoimmune thyroid disease by activating hexokinase 3 and inducing polarization of macrophages towards M1 |
| title_full_unstemmed | High iodine promotes autoimmune thyroid disease by activating hexokinase 3 and inducing polarization of macrophages towards M1 |
| title_short | High iodine promotes autoimmune thyroid disease by activating hexokinase 3 and inducing polarization of macrophages towards M1 |
| title_sort | high iodine promotes autoimmune thyroid disease by activating hexokinase 3 and inducing polarization of macrophages towards m1 |
| topic | autoimmune thyroid disease graves’ disease hashimoto’s thyroiditis macrophage polarization iodine hexokinase 3 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1009932/full |
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