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Publication : Indoleamine 2,3-dioxygenase 1 is essential for sustaining durable antibody responses.

First Author  Lightman SM Year  2021
Journal  Immunity Volume  54
Issue  12 Pages  2772-2783.e5
PubMed ID  34788602 Mgi Jnum  J:318744
Mgi Id  MGI:6856541 Doi  10.1016/j.immuni.2021.10.005
Citation  Lightman SM, et al. (2021) Indoleamine 2,3-dioxygenase 1 is essential for sustaining durable antibody responses. Immunity 54(12):2772-2783.e5
abstractText  Humoral immunity is essential for protection against pathogens, emphasized by the prevention of 2-3 million deaths worldwide annually by childhood immunizations. Long-term protective immunity is dependent on the continual production of neutralizing antibodies by the subset of long-lived plasma cells (LLPCs). LLPCs are not intrinsically long-lived, but require interaction with LLPC niche stromal cells for survival. However, it remains unclear which and how these interactions sustain LLPC survival and long-term humoral immunity. We now have found that the immunosuppressive enzyme indoleamine 2,3- dioxygenase 1 (IDO1) is required to sustain antibody responses and LLPC survival. Activation of IDO1 occurs upon the engagement of CD80/CD86 on the niche dendritic cells by CD28 on LLPC. Kynurenine, the product of IDO1 catabolism, activates the aryl hydrocarbon receptor in LLPC, reinforcing CD28 expression and survival signaling. These findings expand the immune function of IDO1 and uncover a novel pathway for sustaining LLPC survival and humoral immunity.
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