Hobit expression by a subset of human liver-resident CD56^bright Natural Killer cells

Immune responses show a high degree of tissue specificity shaped by factors influencing tissue egress and retention of immune cells. The transcription factor Hobit was recently shown to regulate tissue-residency in mice. Whether Hobit acts in a similar capacity in humans remains unknown. Our aim was to assess the expression and contribution of Hobit to tissue-residency of Natural Killer (NK) cells in the human liver. The human liver was enriched for CD56^bright NK cells showing increased expression levels of the transcription factor Hobit. Hobit^pos CD56^bright NK cells in the liver exhibited high levels of CD49a, CXCR6 and CD69. Hobit^pos CD56^bright NK cells in the liver furthermore expressed a unique set of transcription factors with higher frequencies and levels of T-bet and Blimp-1 when compared to Hobit^neg CD56^bright NK cells. Taken together, we show that the transcription factor Hobit identifies a subset of NK cells in human livers that express a distinct set of adhesion molecules and chemokine receptors consistent with tissue residency. These data suggest that Hobit is involved in regulating tissue-residency of human intrahepatic CD56^bright NK cells in a subset of NK cells in inflamed livers.