2. Academic Validation
  3. FLT3+ DC inhibits immune rejection via interaction with Treg in liver transplantation

FLT3+ DC inhibits immune rejection via interaction with Treg in liver transplantation

  • Int Immunopharmacol. 2024 Jun 17:137:112289. doi: 10.1016/j.intimp.2024.112289.
Jin-Ming Zhang 1,  Hao Huang 1,  Xin-Qiang Li 2,  Shi-Peng Li 3,  Liu-Xin Zhou 1,  Si-Yuan Song 4,  Zhi-Jun Zhu 5
Affiliations

Affiliations

  • 1 Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Clinical Research Center for Pediatric Liver Transplantation of Capital Medical University, Beijing, China; National Clinical Research Center for Digestive Diseases, Beijing, China.
  • 2 Organ Transplantation Center, Affiliated Hospital of Qingdao University, Qingdao, China.
  • 3 Department of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou 450003, China.
  • 4 Baylor College of Medicine, Houston, TX, USA.
  • 5 Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Clinical Research Center for Pediatric Liver Transplantation of Capital Medical University, Beijing, China; National Clinical Research Center for Digestive Diseases, Beijing, China. Electronic address: zhu-zhijun@outlook.com.
PMID: 38889505 DOI: 10.1016/j.intimp.2024.112289
Abstract

Fms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase (RTK) primarily expressed in hematopoietic stem cells and dendritic cells (DCs). While FLT3 plays a critical role in the proliferation, development and maintenance of DCs, thus influencing immune responses under both normal and pathological conditions, there also exists some evidence that FLT3+DC may be involved with immune responses in liver transplantation (LT). In this study, results from single-cell Sequencing data analysis revealed a clear relationship between FLT3+DCs and Regulatory T cells (Tregs) in liver tissue of LT recipients. In peripheral blood samples of LT patients, levels of FLT3+DCs were decreased post-LT-surgery, while Tregs were increased. In a LT mouse model, levels of FLT3+DCs in the liver and bone marrow exhibited an initial time-dependent decrease followed by an increase after LT surgery. Results as obtained with co-culture experiments using mature BMDCs and CD4+ T cells revealed fluctuations in Tregs in response to FLT3 inhibitors and the FLT3 ligand. These findings suggest that FLT3+DCs could emerge as a novel target for mitigating immune rejection in LT.

Keywords

Dendritic Cells (DCs); FLT3; FLT3L; Immunological Mechanisms; Liver Transplantation; Regulatory T cells (Tregs).

Figures
Products