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.
Jodi L Karnell  1 ,  Sadiye Amcaoglu Rieder  2 ,  Rachel Ettinger  3 ,  Roland Kolbeck  4
Affiliations
  • 1. Viela Bio, Gaithersburg, MD 20878, United States.
  • 2. MedImmune, Gaithersburg, MD 20878, United States.
  • 3. Viela Bio, Gaithersburg, MD 20878, United States. Electronic address: [email protected].
  • 4. MedImmune, Gaithersburg, MD 20878, United States. Electronic address: [email protected].
PMID: 30552917 DOI: 10.1016/j.addr.2018.12.005
Abstract

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.
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