Interleukin-35 Prevents the Elevation of the M1/M2 Ratio of Macrophages in Experimental Type 1 Diabetes
Macrophages play an important role in the early development of type 1 diabetes (T1D). Based on the phenotype, macrophages can be classified into pro-inflammatory (M1) and anti-inflammatory (M2) macrophages. Despite intensive research in the field of macrophages and T1D, the kinetic response of M1/M2...
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| author | Zhengkang Luo Charlotte Soläng Rasmus Larsson Kailash Singh |
| author_facet | Zhengkang Luo Charlotte Soläng Rasmus Larsson Kailash Singh |
| author_sort | Zhengkang Luo |
| collection | DOAJ |
| description | Macrophages play an important role in the early development of type 1 diabetes (T1D). Based on the phenotype, macrophages can be classified into pro-inflammatory (M1) and anti-inflammatory (M2) macrophages. Despite intensive research in the field of macrophages and T1D, the kinetic response of M1/M2 ratio has not been studied in T1D. Thus, herein, we studied the M1 and M2 macrophages in the early development of T1D using the multiple low dose streptozotocin (MLDSTZ) mouse model. We determined the proportions of M1 and M2 macrophages in thymic glands, pancreatic lymph nodes and spleens on days 3, 7 and 10 after the first injection of STZ. In addition, we investigated the effect of IL-35 in vivo on the M1/M2 ratio and IL-35<sup>+</sup> plasmacytoid dendritic cells in diabetic mice and in vitro on the sorted macrophages. Our results revealed that the M1/M2 ratio is higher in STZ-treated mice but this was lowered upon the treatment with IL-35. Furthermore, IL-35 treated mice had lower blood glucose levels and a higher proportion of IL-35<sup>+</sup> cells among pDCs. Macrophages treated with IL-35 in vitro also had a higher proportion of M2 macrophages. Together, our data indicate that, under diabetic conditions, pro-inflammatory macrophages increased, but IL-35 treatment decreased the pro-inflammatory macrophages and increased anti-inflammatory macrophages, further suggesting that IL-35 prevents hyperglycemia by maintaining the anti-inflammatory phenotype of macrophages and other immune cells. Thus, IL-35 should be further investigated for the treatment of T1D and other autoimmune disorders. |
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| id | doaj.art-0bc9cef07dd842b0a25a5a6b67ccd411 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T03:20:01Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0bc9cef07dd842b0a25a5a6b67ccd4112023-12-03T15:10:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012314797010.3390/ijms23147970Interleukin-35 Prevents the Elevation of the M1/M2 Ratio of Macrophages in Experimental Type 1 DiabetesZhengkang Luo0Charlotte Soläng1Rasmus Larsson2Kailash Singh3Department of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenDepartment of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenDepartment of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenDepartment of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenMacrophages play an important role in the early development of type 1 diabetes (T1D). Based on the phenotype, macrophages can be classified into pro-inflammatory (M1) and anti-inflammatory (M2) macrophages. Despite intensive research in the field of macrophages and T1D, the kinetic response of M1/M2 ratio has not been studied in T1D. Thus, herein, we studied the M1 and M2 macrophages in the early development of T1D using the multiple low dose streptozotocin (MLDSTZ) mouse model. We determined the proportions of M1 and M2 macrophages in thymic glands, pancreatic lymph nodes and spleens on days 3, 7 and 10 after the first injection of STZ. In addition, we investigated the effect of IL-35 in vivo on the M1/M2 ratio and IL-35<sup>+</sup> plasmacytoid dendritic cells in diabetic mice and in vitro on the sorted macrophages. Our results revealed that the M1/M2 ratio is higher in STZ-treated mice but this was lowered upon the treatment with IL-35. Furthermore, IL-35 treated mice had lower blood glucose levels and a higher proportion of IL-35<sup>+</sup> cells among pDCs. Macrophages treated with IL-35 in vitro also had a higher proportion of M2 macrophages. Together, our data indicate that, under diabetic conditions, pro-inflammatory macrophages increased, but IL-35 treatment decreased the pro-inflammatory macrophages and increased anti-inflammatory macrophages, further suggesting that IL-35 prevents hyperglycemia by maintaining the anti-inflammatory phenotype of macrophages and other immune cells. Thus, IL-35 should be further investigated for the treatment of T1D and other autoimmune disorders.https://www.mdpi.com/1422-0067/23/14/7970type 1 diabetesmacrophages (M1 and M2)pDCsIL-35 |
| spellingShingle | Zhengkang Luo Charlotte Soläng Rasmus Larsson Kailash Singh Interleukin-35 Prevents the Elevation of the M1/M2 Ratio of Macrophages in Experimental Type 1 Diabetes International Journal of Molecular Sciences type 1 diabetes macrophages (M1 and M2) pDCs IL-35 |
| title | Interleukin-35 Prevents the Elevation of the M1/M2 Ratio of Macrophages in Experimental Type 1 Diabetes |
| title_full | Interleukin-35 Prevents the Elevation of the M1/M2 Ratio of Macrophages in Experimental Type 1 Diabetes |
| title_fullStr | Interleukin-35 Prevents the Elevation of the M1/M2 Ratio of Macrophages in Experimental Type 1 Diabetes |
| title_full_unstemmed | Interleukin-35 Prevents the Elevation of the M1/M2 Ratio of Macrophages in Experimental Type 1 Diabetes |
| title_short | Interleukin-35 Prevents the Elevation of the M1/M2 Ratio of Macrophages in Experimental Type 1 Diabetes |
| title_sort | interleukin 35 prevents the elevation of the m1 m2 ratio of macrophages in experimental type 1 diabetes |
| topic | type 1 diabetes macrophages (M1 and M2) pDCs IL-35 |
| url | https://www.mdpi.com/1422-0067/23/14/7970 |
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