Deficiency of the CD155-CD96 immune checkpoint controls IL-9 production in giant cell arteritis.

ABSTRACT: Loss of function of inhibitory immune checkpoints, unleashing pathogenic immune responses, is a potential risk factor for autoimmune disease. Here, we report that patients with the autoimmune vasculitis giant cell arteritis (GCA) have a defective CD155-CD96 immune checkpoint. Macrophages from patients with GCA retain the checkpoint ligand CD155 in the endoplasmic reticulum (ER) and fail to bring it to the cell surface. CD155^low antigen-presenting cells induce expansion of CD4⁺CD96⁺ T cells, which become tissue invasive, accumulate in the blood vessel wall, and release the effector cytokine interleukin-9 (IL-9). In a humanized mouse model of GCA, recombinant human IL-9 causes vessel wall destruction, whereas anti-IL-9 antibodies efficiently suppress innate a

SUBMITTER: Ohtsuki S 

PROVIDER: S-EPMC10140609 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature