Pathway enrichment analysis identifies the FOXO pathway as essential for T cell licensing

Authors

• G SHI
• V NAGARAJAN
• R CASPI

Abstract

It has long been known that during induction of autoimmune central nervous system (CNS) inflammation in animals by adoptive transfer of antigen-specific CD4 T cells, clinical and histological changes do not develop immediately after cell transfer; instead, there is a latent period of at least three days, regardless of the number of cells injected. Odoardi et al. (2012) suggested that this latent period involves a process of "T cell licensing”, during which antigen-specific CD4 T cells acquire pathogenicity. They reported that the transferred T cells accumulated in the lung, where they underwent significant changes in gene expression to facilitate invasion of the CNS. We recently performed Pathway Enrichment Analysis on Odoardi et al.'s published data using the most updated tools and databases. Our analysis identified the FOXO pathway as a critical player in the process of T cell licensing. This pathway mediates a phenotype change during the licensing process, wherein the transferred cells switch from a proliferative phenotype to a pro-inflammatory phenotype with up-regulated expression of S1pr1 and IL7r. The licensed CD4 T cells use S1pr1 to egress from the lung into the blood stream, permitting them to target the CNS. Of note, IL7r has been associated with an increased risk of human multiple sclerosis. An In-depth analysis of this pathway may greatly enhance our understanding of the underlying mechanism of T cell licensing.

Scientific Focus Area: Immunology

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