IL-23 promotes autoimmune Th17 memory formation and function (59.6)

Abstract

Abstract IL-23 is essential for the differentiation of pathogenic effector Th17 cells, but little is known about its requirement in memory Th17 responses. To investigate autoimmune Th17 memory, we developed a variation of the experimental autoimmune encephalomyelitis model, in which CD4+ T cells from MOG(35-55)-immunized donors were transferred into naïve recipients and rested before re-challenge. Following secondary recall, memory Th17 cells rapidly expanded in lymph nodes before trafficking to the central nervous system in high numbers, resulting in earlier onset and increased severity of clinical signs. Th17 memory cells were generated from IL-17+ and RORγt+ precursors, and stability of the Th17 phenotype was dependent on time. IL-23 was required during the primary response for generation of Th17 memory cells During the recall response, IL-17 production was not directly impacted by neutralizing IL-23R at secondary challenge, but the generation of effectors that co- expressed T-bet was strongly impaired. In addition, IL-23R blockade resulted in decreased proliferation and reduced total numbers of Th17 memory cells in the secondary response.