Figure 4. Methods and targets for cellular engineering of trained immunity.

(A) As we use screening tools to elucidate the role of trained innate cells in additional autoimmune and inflammatory disorders, this concept will have increasingly more applications when designing therapeutics, including the activation and suppression of training programs. (B) Trained chimeric antigen receptor (CAR):-Macs generated ex vivo could resist immunosuppression of the tumor microenvironment to promote tumor cell death. (C) For example, trained immunity in atherosclerosis has been shown to contribute to disease pathogenesis and appears to be NLRP3 dependent (Netea et al., 2016; Moorlag et al., 2020). Knocking down NLRP3 expression in patient macrophages could decrease disease burden. This figure was created with BioRender.com.