Session Name: Innate Immunity; Chemokines, Cytokines, Complement
Session Date & Time: None. Available on demand.
*Purpose: Myeloid derived suppressor cells (MDSCs) expand in response to inflammatory stimuli and have been shown to suppress adaptive immunity. Preliminary data from our lab suggests that adjuvant treatment expands MDSCs that can suppress allograft rejection. We hypothesized that distinct phenotypic and functional changes occur in bone marrow myeloid compartment that lead to the production of MDSCs following adjuvant treatment.
*Methods: C57Bl/6 mice were injected with 200 μl saline or alum intraperitoneally every other day for a total of 3 doses. Spleen, peripheral blood and bone marrow was examined at different time points via flow cytometry from either saline or alum treated mice. A separate aliquot of cells were stimulated with PMA (50 ng/mL) and ionomycin (1 ug/mL) and analyzed for the presence of IL-10 via flow cytometry.
*Results: At 7 days post adjuvant treatment, we noted an expansion of common myeloid progenitors (0.28 ± 0.044% vs 0.108 ± 0.013%, p=0.009), macrophage and DC progenitors (0.053 ± 0.010% vs 0.023 ± 0.003%, p=0.034) and common monocyte progenitors (0.62 ± 0.080% vs 0.39 ± 0.033%, p=0.038) in the bone marrow compared to saline controls. In alum treated animals, both monocytic (m)-MDSCs and granulocytic (g)-MDSCs significantly expanded in bone marrow, spleen, and peripheral blood and demonstrated significantly lower expression of CX3CR1 but increased expression of PD-L1, suggestive of a more suppressive phenotype. To support this, alum treatment increased IL-10 production by both M-MDSCs (34.37 ± 4.26 vs 11.32 ± 2.18%, p=0.028) and G-MDSCs (28.6 ± 2.54 vs 5.88 ± 1.46 %, p=0.007) in response to PMA stimulation compared to saline controls
*Conclusions: Adjuvant treatment skews the bone marrow myeloid compartment towards a potent suppressor phenotype. These data support our previous findings that adjuvant treatment can expand m-MDSCs and g-MDSCs that suppress adaptive immunity and allograft rejection. Our data suggest that adjuvants can be designed to selectively expand suppressor cell populations in vivo by shaping the bone marrow compartment. Further, this strategy could be utilized to condition transplant recipient preoperatively and decrease the significant morbidity associated with current immunosuppressive regimens.
To cite this abstract in AMA style:Ge J, Anderson E, Markmann JF, Cuenca A. Adjuvant Treatment Shapes the Bone Marrow Myeloid Compartment Towards an Immunosuppressive Phenotype That Can Suppress Allograft Rejection [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/adjuvant-treatment-shapes-the-bone-marrow-myeloid-compartment-towards-an-immunosuppressive-phenotype-that-can-suppress-allograft-rejection/. Accessed June 13, 2021.
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