Dexamethasone-Induced MerTK^+/high M2c Macrophages Exhibit a Preference for Downregulated Gene Expression Profiles

In a prior study, adoptive cell transfer (ACT) of Dexamethasone (DEX)-induced M2c macrophages with positive expression of MerTK receptor mitigated acute allograft rejection, which was observed in the presence of apoptotic lymphocytes, while simultaneously reducing MHC-II and CD8⁺ T cells in the recipients. However, there has been limited exploration of the properties of adoptive M2c cells, leaving their potential for other applications unclear. In this study, we aimed to characterize the transcriptome profile of DEX-induced MerTK^+/high M2c macrophages. Notably, through the analysis of differentially expressed genes (DEGs), no significant pathway could be constructed from the upregulated DEGs. Only downregulated DEGs could facilitate KEGG construction, encompassing the role of DEX-induced MerTK^+/high M2c in immune tolerance. The expression of T-cell activation, pro- and anti-inflammatory cytokines modulation, leukocyte recruitment and adjustment of MHC-I/II-related proteins were entirely diminished. Nonetheless, association of these traits suggests the potential of MerTK^+/high M2c macrophages for use in ACT, particularly for autoimmune conditions such as rheumatoid arthritis, inflammatory bowel disease, type-I diabetes mellitus, and AGE/RAGE signaling pathway in diabetic complications. In summary, the preference for downregulated gene expression profiles in DEX-induced MerTK^+/high M2c macrophages affirms their potential for immunosuppressive adoptive cell therapy.