TLR3 Agonist Amplifies the Anti‐Inflammatory Potency of ADSCs via IL‐10‐Mediated Macrophage Polarization in Acute Pancreatitis

Abstract

The immunoregulatory role of mesenchymal stem cells (MSCs) in inflammation is heterogeneous and can exhibit anti‐inflammatory or proinflammatory properties depending on the microenvironment. We herein observed that the activation of Toll‐like receptor 3 (TLR3) by polyinosinic : polycytidylic acid (poly(I : C)) stimulation facilitated the transformation of adipose‐derived stem cells (ADSCs) into an anti‐inflammatory phenotype. The enhanced anti‐inflammatory properties were assessed in a taurocholate‐induced pancreatitis model. The results demonstrated that poly(I : C) pretreated ADSCs exhibited enhanced anti‐inflammatory properties than untreated ADSCs in taurocholate‐induced pancreatitis. Mechanistically, poly(I : C)‐treated ADSCs showed increased production and secretion of interleukin‐10 (IL‐10), which demonstrates a potent ability to alleviate inflammatory signaling cascades in acinar cells. Simultaneously, the heightened anti‐inflammatory effects of poly(I : C)‐treated ADSCs in pancreatitis were associated with the regulation of macrophage classical/alternative transformation, thereby mitigating inflammatory factor‐mediated damage to the pancreatic acinar cell. We propose that TLR3 activation by poly(I : C) is an effective strategy to enhance the anti‐inflammatory properties of MSCs, which offers a valuable consideration for improving the therapeutic efficacy of MSCs in inflammatory diseases.