Targeting the CD40-CD40L pathway in autoimmune diseases: Humoral immunity and beyond

Adv Drug Deliv Rev. 2019 Feb 15:141:92-103. doi: 10.1016/j.addr.2018.12.005. Epub 2018 Dec 13.


CD40 is a TNF receptor superfamily member expressed on both immune and non-immune cells. Interactions between B cell-expressed CD40 and its binding partner, CD40L, predominantly expressed on activated CD4+ T cells, play a critical role in promoting germinal center formation and the production of class-switched antibodies. Non-hematopoietic cells expressing CD40 can also engage CD40L and trigger a pro-inflammatory response. This article will highlight what is known about the biology of the CD40-CD40L axis in humans and describe the potential contribution of CD40 signaling on both hematopoietic and non-hematopoietic cells to autoimmune disease pathogenesis. Additionally, novel therapeutic approaches to target this pathway, currently being evaluated in clinical trials, are discussed.

Keywords: Autoimmunity; CD40-CD40L pathway; Cell-mediated immunity; Germinal center; Humoral immunity; Novel therapeutics.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology
  • CD40 Antigens / immunology*
  • CD40 Ligand / immunology*
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Signal Transduction


  • CD40 Antigens
  • CD40 Ligand