M-MDSC in vitro generation from mouse bone marrow with IL-3 reveals high expression and functional activity of arginase 1
Please always quote using this URN: urn:nbn:de:bvb:20-opus-317769
- Myeloid-derived suppressor cells (MDSC) represent major regulators of immune responses, which can control T cells via their inducible nitric oxide synthase (iNOS)- and arginase 1 (Arg1)-mediated effector functions. While GM-CSF is well documented to promote MDSC development, little is known about this potential of IL-3, an established growth factor for mast cells. Here, we show that IL-3, similar to GM-CSF, generates monocytic MDSC (M-MDSC) from murine bone marrow (BM) cells after 3 days of in vitro culture. At this time point, predominantlyMyeloid-derived suppressor cells (MDSC) represent major regulators of immune responses, which can control T cells via their inducible nitric oxide synthase (iNOS)- and arginase 1 (Arg1)-mediated effector functions. While GM-CSF is well documented to promote MDSC development, little is known about this potential of IL-3, an established growth factor for mast cells. Here, we show that IL-3, similar to GM-CSF, generates monocytic MDSC (M-MDSC) from murine bone marrow (BM) cells after 3 days of in vitro culture. At this time point, predominantly CD11b+ CD49a+ monocytic and CD11b+ CD49a- FcεR I- neutrophilic cells were detectable, while CD11blow/neg FcεR I+ mast cells accumulated only after extended culture periods. Both growth factors were equivalent in generating M-MDSC with respect to phenotype, cell yield and typical surface markers. However, IL-3 generated M-MDSC produced less TNF, IL-1β and IL-10 after activation with LPS + IFN-γ but showed higher Arg1 expression compared to GM-CSF generated M-MDSC. Arg1 was further induced together with iNOS after MDSC activation. Accordingly, an increased Arg1-dependent suppressor activity by the IL-3 generated M-MDSC was observed using respective iNOS and Arg1 inhibitors. Together, these data indicate that M-MDSC can be generated in vitro by IL-3, similar to GM-CSF, but with increased Arg1 expression and Arg1-mediated suppression capacity. This protocol now allows further in vitro studies on the role of IL-3 for MDSC biology.…
Author: | Arpa Aintablian, Sandra Strozniak, Marion Heuer, Manfred B. Lutz |
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URN: | urn:nbn:de:bvb:20-opus-317769 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Institut für Virologie und Immunbiologie |
Language: | English |
Parent Title (English): | Frontiers in Immunology |
Year of Completion: | 2023 |
Volume: | 14 |
Article Number: | 1130600 |
Source: | Frontiers in Immunology (2023) 14:1130600. https://doi.org/10.3389/fimmu.2023.1130600 |
DOI: | https://doi.org/10.3389/fimmu.2023.1130600 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | GM-CSF; IL-3; bone marrow; in vitro culture; myeloid-derived suppressor cells (MDSC); protocol |
Release Date: | 2024/05/31 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |