Targeting the CCL2-CCR2 axis with ursodeoxycholic acid attenuates monocyte migration and platelet clearance in immune thrombocytopenia.

Abstract

Immune thrombocytopenia (ITP) is an autoimmune condition characterized by the destruction of platelets or their inadequate production due to immune system dysregulation. Ursodeoxycholic acid (UDCA) exhibits anti-inflammatory and immunomodulatory effects; however, its specific mechanism of action in the context of ITP remains to be fully elucidated. The present study aimed to examine the impact of UDCA on monocyte migration and to elucidate the underlying molecular mechanisms through transcriptomic analyses complemented by both in vivo and in vitro experiments. The findings revealed that UDCA markedly inhibited the migration of monocytes from the bone marrow into the peripheral circulation in an ITP murine model, concomitantly reducing the population of M1 macrophages within the spleen and their capacity for platelet phagocytosis. In vitro assays demonstrated that UDCA suppressed the migration of THP-1 monocytes, an effect contingent upon the CCL2-CCR2 chemokine axis. Mechanistic investigations indicated that UDCA downregulated the expression of CCR2 (C-C chemokine receptor 2) and modulated the activity of the p38/ERK and AKT signaling pathways. This study provides the first evidence that UDCA attenuates the pathological progression of ITP by inhibiting monocyte migration via the CCL2-CCR2 chemokine pathway, thereby offering novel theoretical insights to support its clinical application.