Tissue-resident Eomes+ NK cells are the major innate lymphoid cell population in human infant intestine

Adrian F Sagebiel,Renée R C E Schreurs,Christian Körner,Madeleine J Bunders,Konrad Reinshagen,Daniel Perez,Marcus Altfeld,Sebastian Lunemann,Fenja Steinert

doi:10.1038/s41467-018-08267-7

Abstract

Innate lymphoid cells (ILC), including natural killer (NK) cells, are implicated in host-defense and tissue-growth. However, the composition and kinetics of NK cells in the intestine during the first year of life, when infants are first broadly exposed to exogenous antigens, are still unclear. Here we show that CD103+ NK cells are the major ILC population in the small intestines of infants. When compared to adult intestinal NK cells, infant intestinal NK cells exhibit a robust effector phenotype, characterized by Eomes, perforin and granzyme B expression, and superior degranulation capacity. Absolute intestinal NK cell numbers decrease gradually during the first year of life, coinciding with an influx of intestinal Eomes+ T cells; by contrast, epithelial NKp44+CD69+ NK cells with less cytotoxic capacity persist in adults. In conclusion, NK cells are abundant in infant intestines, where they can provide effector functions while Eomes+ T cell responses mature.

Highlights

Innate lymphoid cells (ILC), including natural killer (NK) cells, are implicated in host-defense and tissue-growth
We demonstrate that CD127−CD103+Eomes+ NK cells are the major ILC population in infant intestines during the first months of life, and that their absolute numbers decrease with age
An increasing number of studies have shown that ILCs, including NK cells, are critical in host defense and can mediate tissue modeling[6,8,9,10,12,13,38,45]

Summary

Introduction

Innate lymphoid cells (ILC), including natural killer (NK) cells, are implicated in host-defense and tissue-growth. When compared to adult intestinal NK cells, infant intestinal NK cells exhibit a robust effector phenotype, characterized by Eomes, perforin and granzyme B expression, and superior degranulation capacity. Absolute intestinal NK cell numbers decrease gradually during the first year of life, coinciding with an influx of intestinal Eomes+ T cells; by contrast, epithelial NKp44+CD69+ NK cells with less cytotoxic capacity persist in adults. The composition and kinetics of NK cells in intestines during the first year of life, when infants are exposed to exogenous antigens and have a high susceptibility to viral infections, are still unclear[21]. Infant intestinal NK cells exhibit a cytotoxic phenotype compared with adult intestinal NK cells, and have higher perforin and granzyme B expression combined with superior capacity to degranulate. The first year of life features dynamic changes in the lymphocyte compartment, shifting from Eomes+ NK cells to Eomes+ T cells in human intestines

Methods

Results

Conclusion