Interleukin-10-engineered mesenchymal stem/stromal cells exhibit robust immunomodulatory effects in vitro and in vivo

• MSC-IL-10 maintained mesenchymal phenotype and multipotency while exhibiting robust IL-10 expression. • MSC-IL-10 significantly reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-12) and Nos2 expression in vitro, outperforming wild-type MSCs. • In LPS-induced endotoxemia, MSC-IL-10 reduced systemic inflammation, restored leukocyte counts, and attenuated CD11b⁺ cell recruitment. • MSC-IL-10 mitigated tissue damage, particularly in lungs, and biodistributed to liver, lungs, and spleen, supporting its therapeutic potential for sepsis.