Uterine Tissue-Resident Natural Killer Cells Derived from Conventional Natural Killer Cells are

Regulated by Progesterone

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Presentation Time: 01:45 PM - 02:00 PM
Abstract ID: 6082 - A

Presenting Author:
Dorothy K. Sojka , Assistant Professor at Loyola Univ. Chicago

Abstract:

Innate lymphoid cells (ILCs) respond to pathogen-induced tissue distress and maintain tissue homeostasis. The uterus contains three subsets of ILCs: ILC1, conventional natural killer (cNK) cells, and tissue-resident NK (trNK) cells. ILC1s and cNK cells seed the uterus before puberty. In contrast, trNK cells emerge at the onset of puberty and persist with varied frequency throughout the estrous cycle. Here, we considered the origin of uterine trNK cells and the potential influence of hormones on their differentiation in the uterus. We intravascularly labeled immune cells to distinguish cells in the vasculature by flow cytometry of ovariectomized (OVX) mice supplemented with hormones, intact and parabiosed mice. We found that mice OVX at three weeks of age and analyzed as adults did not have trNK cells in the uterine tissue unless progesterone (P4) was administered. In parabiosed mice, we identified cNK-derived trNK cells in estrous cycling but not in the noncycling parabionts. Delivery of P4 to OVX or intact mice induced the expansion of cNK-derived trNK cells which was abrogated if RU486 was administered. Uterine ILCs from Nfil3^-/- mice, that lack cNK cells, did not expand in response to P4. Finally, sorted cNK cells transferred into OVX mice supplemented with P4 differentiated into trNK cells in the uterus, but not the spleen. Taken together, we identified a novel differentiation pathway for uterine trNK cells tightly regulated by P4 in the uterine tissue.