The transcription factor Foxp1 regulates the differentiation and function of dendritic cells

Mech Dev. 2019 Aug:158:103554. doi: 10.1016/j.mod.2019.05.001. Epub 2019 May 8.

Abstract

Dendritic cells (DCs) are the sentinels of the immune system and play a critical role in initiating adaptive immune responses against pathogens. As the most powerful antigen presenting cells, DCs are also important in maintaining immune homeostasis and participating in the development of autoimmune diseases. How the maturation and function of DCs is regulated in these conditions and what is the function of various transcription factors is still unclear. In this study, we found that the expression of the transcription factor Foxp1 gradually increased during the maturation of DCs. Then, we constructed a recombinant adenovirus carrying Foxp1-interfering RNA (Ad-simFoxp1) and transfected murine bone marrow-derived DCs in vitro. DCs transfected with Ad-simFoxp1 exhibited markedly lower costimulatory molecules, and decreased cytokines. And Ad-simFoxp1 greatly inhibited mature DC-induced T cell responses. Moreover, in vivo infusion with Ad-simFoxp1-modified DCs significantly delayed the onset of experimental autoimmune encephalomyelitis (EAE). Therefore, adoptive transfection of Ad-simFoxp1 in DCs may be a potential treatment strategy against autoimmune diseases.

Keywords: Dendritic cells; EAE; Foxp1; autoimmune disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Bone Marrow Cells / cytology
  • Cell Differentiation*
  • Cell Proliferation
  • Cytokines / metabolism
  • Dendritic Cells / cytology*
  • Dendritic Cells / metabolism*
  • Disease Progression
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Forkhead Transcription Factors / metabolism*
  • Gene Silencing
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Phagocytosis
  • Repressor Proteins / metabolism*

Substances

  • Cytokines
  • Forkhead Transcription Factors
  • Foxp1 protein, mouse
  • Repressor Proteins