Hobit expression by a subset of human liver-resident CD56bright 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.