Abstract
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 CD56bright NK cells showing increased expression levels of the transcription factor Hobit. Hobitpos CD56bright NK cells in the liver exhibited high levels of CD49a, CXCR6 and CD69. Hobitpos CD56bright 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 Hobitneg CD56bright 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 CD56bright NK cells in a subset of NK cells in inflamed livers.
Highlights
The quality of immune responses is influenced by a plethora of factors
CD56bright Natural Killer (NK) cells are enriched in human liver tissue
Flow cytometric analysis of the samples revealed that the overall frequency of bulk NK cells within the lymphocyte population was slightly higher in human liver samples (Fig. 1a) compared to matched peripheral blood
Summary
The quality of immune responses is influenced by a plethora of factors. There is mounting evidence that tissues are shaping immune responses to serve their specific needs through interactions between immune and tissue cells. Recent studies in humans have shown that some of the markers used to identify tissue-resident NK cells in murine livers, namely CD49a9 and CXCR610, 11, are expressed on human NK cells within the liver. It was shown that CXCR6+ NK cells in human livers exhibited an Eomeshi T-betlo phenotype[10, 11], which is in contrast to the Eomeslo T-betint phenotype initially described for CD49a+ NK cells in the liver[9]. This might suggest that several heterogeneous subsets of liver-resident NK cells exist in human livers. We investigated Hobit expression by human NK cells and its role in regulating tissue-residency of intrahepatic NK cells
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