aTyr Pharma Provides Mechanistic Update on Resokine Pathway at American Academy of Immunology Annual Meeting
Title: “Identification of a T cell Immunomodulatory Domain in Histidyl-tRNA Synthetase”
- ATYR1940 reduced human T cell activation as indicated by lower surface expression of activation markers and decreased release of Th1, Th2, and Th17 cytokines.
- Effects were observed on naïve and effector/memory T cells as well as on CD4+ and CD8+ subsets.
- Gene profiling studies confirmed that ATYR1940 reduced T cell activation and sustained expression of genes that maintain T cells in a resting state.
- The iMod domain of ATYR1940 was responsible for mediating immunomodulatory function.
- The iMod domain and ATYR1923 also reduced T cell activation and cytokine release from stimulated T cells.
- These results suggest that HARS may function as a circulating immune set-point modulator through action by its iMod domain.
About the Resokine Pathway
The Resokine pathway is comprised of extracellular proteins derived from the histidyl tRNA synthetase (HARS) gene family. The gene for HARS gives rise to a number of splice variants, many of which have lost their catalytic activity, but which retain the N-terminal domain of 59 amino acids. This domain was appended to HARS during evolution of multicellular organisms and is not essential for protein synthetic activity but is retained with high homology across mammalian species. Proteins derived from the HARS gene, both full-length and splice variants, are present in human circulation and appear to play a role in modulating immune responses. We refer to the extracellular HARS proteins as Resokine, to differentiate them from the intracellular enzyme involved in protein synthesis.
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Source: aTyr Pharma, Inc.