On 4 March 2024, Professor Huang Bo's team at the School of Basic Medical Sciences published online in PNAS the latest research titled "Sustained AhR activation signals regulate memory differentiation of early effector CD8+ T cells" research results. This study reveals the key role of the aryl hydrocarbon receptor (AhR) in regulating the formation of memory T cells, and reveals the specific molecular mechanism of how early effector CD8+ T cells are regulated by AhR to differentiate into memory T cells.

Identification of mechanisms that program early effector T cells to either terminal effector T (Teff) or memory T (Tm) cells has important implications for protective immunity against infections and cancers. Here, we show that the cytosolic transcription factor aryl hydrocarbon receptor (AhR) is used by early Teff cells to program memory fate. Upon antigen engagement, AhR is rapidly up-regulated via reactive oxygen species signaling in early CD8+ Teff cells, which does not affect the effector response, but is required for memory formation. Mechanistically, activated CD8+ T cells up-regulate HIF-1α to compete with AhR for HIF-1β, leading to the loss of AhR activity in HIF-1αhigh short-lived effector cells, but sustained in HIF-1αlow memory precursor effector cells (MPECs) with the help of autocrine IL-2. AhR then licenses CD8+ MPECs in a quiescent state for memory formation. These findings partially resolve the long-standing issue of how Teff cells are regulated to differentiate into memory cells.

Paper link:https://pubmed.ncbi.nlm.nih.gov/38437537/