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Functional differences between human NKp44- and NKp44+ RORC+ innate lymphoid cells

By K. (Kerim) Hoorweg, C.P. (Charlotte) Peters, F.H.J. (Ferry) Cornelissen, P. (Patricia) Aparicio-Domingo, N. (Natalie) Papazian, G. (Geert) Kazemier, J.M. (Jenny) Mjösberg, H. (Hergen) Spits and T. (Tom) Cupedo


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

Topics: Fetal, Human, IL-17a, IL-22, Innate lymphoid cells, Lymph node, RORC, Tonsil
Year: 2012
DOI identifier: 10.3389/fimmu.2012.00072
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