2023-Regulatory macrophages in solid organ xenotransplantatio

Due to a critical organ shortage, pig organs are being explored for use in transplantation.
Differences between species, particularly in cell surface glycans, can trigger
elevated immune responses in xenotransplantation. To mitigate the risk of hyperacute
rejection, genetically modified pigs have been developed that lack certain glycans and
express human complement inhibitors. Nevertheless, organs from these pigs may still
provoke stronger inflammatory and innate immune reactions than allotransplants. Dysregulation
of coagulation and persistent inflammation remain obstacles in the transplantation
of pig organs into primates. Regulatory macrophages (Mregs), known for
their anti-inflammatory properties, could offer a potential solution. Mregs secrete interleukin
10 and transforming growth factor beta, thereby suppressing immune responses
and promoting the development of regulatory T cells. These Mregs are typically induced
via the stimulation of monocytes or macrophages with macrophage colony-stimulating
factor and interferon gamma, and they conspicuously express the stable marker dehydrogenase/
reductase 9. Consequently, understanding the precise mechanisms governing
Mreg generation, stability, and immunomodulation could pave the way for the
therapeutic use of Mregs generated in vitro. This approach has the potential to reduce
the required dosages and durations of anti-inflammatory and immunosuppressive
medications in preclinical and clinical settings