CD40, a member of the TNF receptor superfamily, is expressed on both immune and non-immune cells. Its interaction with CD40L (predominantly expressed on activated CD4+ T cells) is crucial in promoting germinal center formation and class-switched antibody production. This interaction also participates in CD4+ T cell priming by dendritic cells, CD4+ T cell help to B cells, and classical macrophage activation [1,2]. The CD40-CD40L pathway is involved in multiple biological processes related to the immune response.

In autoimmune diseases, the CD40-CD40L axis contributes to the pathogenesis, with non-hematopoietic cells expressing CD40 also able to trigger a pro-inflammatory response upon engaging CD40L [1]. In the context of type 2 immunity, CD40-CD154 (CD40L) interaction is necessary for most Th2 responses, though its role in helminth infection-related Th2 immunology is still being understood [2]. Additionally, targeting the CD40-CD40L system is being explored as a strategy for treating atherosclerosis, as it plays a role in the immune-inflammation associated with the disease [3].

In conclusion, CD40 is central in immunological processes, playing key roles in antibody production, T cell-related functions, and immune-related diseases. Studies exploring the CD40-CD40L axis in various disease models, especially those related to autoimmunity, type 2 immunity, and atherosclerosis, have provided insights into its functions and potential as a therapeutic target.

References:

1. Karnell, Jodi L, Rieder, Sadiye Amcaoglu, Ettinger, Rachel, Kolbeck, Roland. 2018. Targeting the CD40-CD40L pathway in autoimmune diseases: Humoral immunity and beyond. In Advanced drug delivery reviews, 141, 92-103. doi:10.1016/j.addr.2018.12.005. https://pubmed.ncbi.nlm.nih.gov/30552917/

2. Díaz, Álvaro, González-Alayón, Ignacio, Pérez-Torrado, Valentina, Suárez-Martins, Mariana. 2021. CD40-CD154: A perspective from type 2 immunity. In Seminars in immunology, 53, 101528. doi:10.1016/j.smim.2021.101528. https://pubmed.ncbi.nlm.nih.gov/34810089/

3. Tian, Simeng, Wang, Yufei, Wan, Jie, Yang, Mao, Fu, Zhenkun. . Co-stimulators CD40-CD40L, a potential immune-therapy target for atherosclerosis: A review. In Medicine, 103, e37718. doi:10.1097/MD.0000000000037718. https://pubmed.ncbi.nlm.nih.gov/38579073/