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AUTOIMMUNITY

Freeing PDL1 alleviates autoimmunity

Nature Reviews Rheumatology volume 18, page 185 (2022)Cite this article

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Immunotherapy with targeted blockade of the inhibitory co-receptor PD1 is now a valuable tool for treating cancer; conversely, targeted potentiation of PD1 is expected to ameliorate autoimmune disease, but achieving this effect has proved elusive. New research published in Nature Immunology demonstrates that PD1 function can be elicited by freeing up its ligand, PDL1, from binding to CD80, thereby improving symptoms of autoimmune disease in animal models.

The researchers generated monoclonal antibodies against mouse and human CD80 (termed TKMG48 and TKMF5, respectively), which physically dissociated the cis-PDL1–CD80 duplex and enabled PD1 to associate with PDL1 on activated dendritic cells (DCs) in the presence of CD80. The PD1–PDL1 association induced by the antibodies enabled PD1 signalling that inhibited T cell activation. In C57BL/6 N mice, TKMG48 was able to increase the PD1-binding capacity of DCs and weaken antigen-specific T cell responses.

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  1. Nature Reviews Rheumatology http://www.nature.com/nrrheum/

    Sarah Onuora

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  1. Sarah Onuora
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Correspondence to Sarah Onuora.

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Onuora, S. Freeing PDL1 alleviates autoimmunity. Nat Rev Rheumatol 18, 185 (2022). https://doi.org/10.1038/s41584-022-00772-w

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  • DOI: https://doi.org/10.1038/s41584-022-00772-w

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