PHGDH regulates dendritic cell immune crosstalk 2267410

Abstract Introduction Conventional dendritic cells (cDCs) play a unique role in immunoregulation and antigen presentation, which is fundamental to protective immunity and is implicated in various autoimmune pathologies. Accordingly, cDCs are targeted in autoimmune and cancer immunotherapies. However, leveraging their full therapeutic potential is limited by an incomplete mechanistic understanding of cDC functions. Methods We used transcriptomic, metabolomic, and immunophenotyping analyses on both in vivo and in vitro cDCs to investigate molecular regulators of cDC immune maturation and T cell stimulation. Results These analyses identified phosphoglycerate dehydrogenase (PHGDH) as a key modulator of cDC immune functions. Loss of PHGDH limits cDC maturation and weakens their ability to prime potent effector CD8+ T cell responses. We show that PHGDH regulates cDC function through a non-canonical mechanism involving remodeling of interactions with bystander cells, such as T cells. Conclusion Our findings identify PHGDH as a critical immunomodulator of cDCs and highlight its potential as a therapeutic target for autoimmune diseases through modulation of cDC-mediated immune crosstalk. Funding Source n/a Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)