title: Functional Differences between Human NKp44(-) and NKp44(+) RORC(+) Innate Lymphoid Cells.
abstract: Human RORC(+) lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines in human homeostasis and disease is hampered by a poor characterization of RORC(+) innate cell subsets and a lack of knowledge on the distribution of these cells in adults. Here we show that functionally distinct subsets of human RORC(+) innate lymphoid cells are enriched for secretion of IL-17a or IL-22. Both subsets have an activated phenotype and can be distinguished based on the presence or absence of the natural cytotoxicity receptor NKp44. NKp44(+) IL-22 producing cells are present in tonsils while NKp44(-) IL-17a producing cells are present in fetal developing lymph nodes. Development of human intestinal NKp44(+) ILC is a programmed event that is independent of bacterial colonization and these cells colonize the fetal intestine during the first trimester. In the adult intestine, NKp44(+) ILC are the main ILC subset producing IL-22. NKp44(-) ILC remain present throughout adulthood in peripheral non-inflamed lymph nodes as resting, non-cytokine producing cells. However, upon stimulation lymph node ILC can swiftly initiate cytokine transcription suggesting that secondary human lymphoid organs may function as a reservoir for innate lymphoid cells capable of participating in inflammatory responses.
authors.affiliation: Department of Hematology, Erasmus University Medical Center Rotterdam, Netherlands.
authors.forename: Kerim
authors.initials: K
authors.lastname: Hoorweg
authors.forename: Charlotte P
authors.initials: CP
authors.lastname: Peters
authors.forename: Ferry
authors.initials: F
authors.lastname: Cornelissen
authors.forename: Patricia
authors.initials: P
authors.lastname: Aparicio-Domingo
authors.forename: Natalie
authors.initials: N
authors.lastname: Papazian
authors.forename: Geert
authors.initials: G
authors.lastname: Kazemier
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Mjösberg
authors.forename: Hergen
authors.initials: H
authors.lastname: Spits
authors.forename: Tom
authors.initials: T
authors.lastname: Cupedo