Transcriptional Regulation of Mouse Tissue-Resident Natural Killer Cell Development.

Nuriban Valero-Pacheco,Aimee M Beaulieu

doi:10.3389/fimmu.2020.00309

Nuriban Valero-Pacheco, Aimee M Beaulieu

Open Access

https://doi.org/10.3389/fimmu.2020.00309

Copy DOI

Abstract

Natural killer (NK) cells are cytotoxic innate lymphocytes that are well-known for their ability to kill infected or malignant cells. Beyond their roles in tumor surveillance and anti-pathogen defense, more recent studies have highlighted key roles for NK cells in a broad range of biological processes, including metabolic homeostasis, immunomodulation of T cells, contact hypersensitivity, and pregnancy. Consistent with the breadth and diversity of these functions, it is now appreciated that NK cells are a heterogeneous population, comprised of specialized and sometimes tissue-specific subsets with distinct phenotypes and effector functions. Indeed, in addition to the conventional NK cells (cNKs) that are abundant and have been well-studied in the blood and spleen, distinct subsets of tissue-resident NK cells (trNKs) and “helper” Group 1 innate lymphoid cells (ILC1s) have now been described in multiple organs and tissues, including the liver, uterus, thymus, adipose tissue, and skin, among others. The cNK, trNK, and/or helper ILC1 populations that co-exist in these various tissues exhibit both common and distinct developmental requirements, suggesting that a combination of lineage–, subset–, and tissue–specific differentiation processes may contribute to the unique functional properties of these various populations. Here, we provide an overview of the transcriptional regulatory pathways known to instruct the development and differentiation of cNK, trNK, and helper ILC1 populations in specific tissues in mice.

Highlights

Natural killer (NK) cells are cytotoxic innate lymphocytes that were first identified in 1975 based on their capacity to spontaneously kill tumor cell lines without prior immunization [1, 2]
Recent studies have demonstrated that, like many other immune cell lineages, unique tissue-resident NK and helper ILC1 populations exist in a broad array of tissues and organs
Examples include the immunomodulatory function of salivary glands (SG) tissue-resident NK cells (trNKs) in dampening T cell-mediated tissue damage in the SG during viral infection, and the negative impact of IFN-γ-producing NK and helper ILC1 populations in the adipose tissue on obesityrelated metabolic dysfunction [102, 106,107,108,109,110]

Summary

Introduction

Natural killer (NK) cells are cytotoxic innate lymphocytes that were first identified in 1975 based on their capacity to spontaneously kill tumor cell lines without prior immunization [1, 2]. In addition to circulating CD49a−CD49b+Eomes+ cNKs, the liver harbors a unique population of CD49a+CD49b−Eomes− ILC1s that are tissue-resident in parabiotic mice [58, 59]. At least three distinct NK and/or ILC1 populations exist in the uterus, each with unique transcriptional signatures: CD49a−CD49b+Eomes+ cNKs, tissue-resident CD49a+CD49b−Eomes+ trNKs, and CD49a+CD49b−Eomes− helper ILC1s [73,74,75,76].

Results

Conclusion