Unraveling the early transcriptional signature of peripheral blood NK cell transition to uterine residency

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B176
Abstract ID: 4741

Presenting Author:
Morgan E.C. Greene , Graduate Trainee at Univ. of Alabama, Birmingham

Abstract:

Tissue-resident uterine NK cells are essential for successful pregnancy, yet the molecular mechanisms guiding their tissue residency programming early after infiltration of blood-based precursors remain unknown. We examined the transition of CD56⁺ peripheral blood NK cells to a uterine resident state by performing scRNA-seq on enriched CD56⁺ cells from a matched peripheral blood (pb) and endometrial (e) biopsy taken during the secretory phase. Our integrated analysis comparing eNK vs pbNK cells identified a tissue adaptation signature. Key components of this signature included NR4A2 (94% vs 0%, p=9.46e-22), FOS (90% vs 9%, p=9.05e-14), and JUNB (77% vs 16%, p=3.15e-07) respectively. This signature also mirrored genes previously identified in activated murine intestinal CD8⁺ TRM cells early after LCMV infection. This signature was found in all endometrial CD56⁺ cells, including CD56^bright CD16^- eNKs, NKTs, and conventional eNKs (CD56^dimCD16⁺). Pathway analysis implicated IL-17 and IL-18 cytokines, along with NFAT and VEGF signals in tissue residency programming. In conclusion, these data expand our understanding of early transcriptional programs in lymphocyte tissue adaptation, revealing the involvement of cytokines beyond TGF-β. Our data further indicate that signals associated with early tissue adaptation are conserved across species and cell types independent of an antigen receptor.