2. Academic Validation
  3. Nanoparticle delivery of CD40 siRNA suppresses alloimmune responses by inhibiting activation and differentiation of DCs and macrophages

Nanoparticle delivery of CD40 siRNA suppresses alloimmune responses by inhibiting activation and differentiation of DCs and macrophages

  • Sci Adv. 2022 Dec 21;8(51):eabq3699. doi: 10.1126/sciadv.abq3699.
Jialiang Wang 1 2,  Kuirong Mao 1 2 3,  Xiuxiu Cong 1 2,  Huizhu Tan 1 2,  Chenxi Wu 1,  Zheng Hu 1 2,  Yong-Guang Yang 1 2 3,  Tianmeng Sun 1 2 3 4
Affiliations

Affiliations

  • 1 Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Changchun, Jilin, China.
  • 2 National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, Jilin, China.
  • 3 International Center of Future Science, Jilin University, Changchun, Jilin, China.
  • 4 State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, Jilin, China.
PMID: 36542700 DOI: 10.1126/sciadv.abq3699
Abstract

CD40 is an important costimulatory molecule expressed on antigen-presenting cells (APCs) and plays a critical role for APC activation, offering a promising therapeutic target for preventing allograft rejection. Here, we developed a biodegradable nanoparticle small interfering RNA delivery system (siCD40/NPs) to effectively deliver CD40 siRNA (siCD40) into hematopoietic stem cells (HSCs), myeloid progenitors, and mature dendritic cells (DCs) and macrophages. Injection of siCD40/NPs not only down-regulated CD40 expression in DCs and macrophages but also inhibited the differentiation of HSCs and/or myeloid progenitors into functional DCs and macrophages. Furthermore, siCD40/NPs treatment significantly prolonged allograft survival in mouse models of skin allotransplantation. In addition to reiteration of the role of CD40 in APC activation, our findings highlight a previously unappreciated role of CD40 in DC and macrophage differentiation from their progenitors. Furthermore, our results support the effectiveness of siCD40/NPs in suppressing alloimmune responses, providing a potential means of facilitating tolerance induction and preventing allotransplant rejection.

Figures
Products