TY  - JOUR
A1  - Aintablian, Arpa
A1  - Strozniak, Sandra
A1  - Heuer, Marion
A1  - Lutz, Manfred B.
T1  - M-MDSC in vitro generation from mouse bone marrow with IL-3 reveals high expression and functional activity of arginase 1
T2  - Frontiers in Immunology
N2  - 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, 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.
KW  - myeloid-derived suppressor cells (MDSC)
KW  - bone marrow
KW  - IL-3
KW  - GM-CSF
KW  - in vitro culture
KW  - protocol
Y1  - 2023
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/31776
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-317769
VL  - 14
ER  -