A human NK cell subset provides an innate source of IL-22 for mucosal immunity

By M. Cella, A. Fuchs, W. Vermi, F. Facchetti, K. Otero, J. Lennerz, J. Doherty, J. Mills, M. Colonna. Nature, 2008

1,237 citations recorded by the source corpus.

Natural killer (NK) cells are classically viewed as lymphocytes that provide innate surveillance against virally infected cells and tumour cells through the release of cytolytic mediators and interferon (IFN)-γ. In humans, blood CD56dim NK cells specialize in the lysis of cell targets. In the lymph nodes, CD56bright NK cells secrete IFN-γ cooperating with dendritic cells and T cells in the generation of adaptive responses. Here we report the characterization of a human NK cell subset located in mucosa-associated lymphoid tissues, such as tonsils and Peyer’s patches, which is hard-wired to secrete interleukin (IL)-22, IL-26 and leukaemia inhibitory factor. These NK cells, which we refer to as NK-22 cells, are triggered by acute exposure to IL-23. In vitro, NK-22-secreted cytokines stimulate epithelial cells to secrete IL-10, proliferate and express a variety of mitogenic and anti-apoptotic molecules. NK-22 cells are also found in mouse mucosa-associated lymphoid tissues and appear in the small intestine lamina propria during bacterial infection, suggesting that NK-22 cells provide an innate source of IL-22 that may help constrain inflammation and protect mucosal sites.

Subfields: Immunology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/623b00af1f5bfb70e83eab6e28568b1c0b1733fa

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In Immunology

1. D. Artis
2. F. Sallusto
3. C. Garlanda
4. A. Lanzavecchia
5. H. Spits
6. F. Powrie
7. M. Colonna
8. Brigitta Stockinger

In Pathology and Forensic Medicine

1. F. Powrie
2. M. V. D. van den Brink
3. H. Spits
4. D. Cua
5. J. Dudakov
6. A. Hanash

Citations in the corpus

• Genetics and pathogenesis of inflammatory bowel disease (2011, background): “Produced by several cell types, such as ILCs, lymphoid tissue induced (LTi) cells, T H 17 cells and γδ T cells, most intestinal IL-22 at steady state is produced by ILCs expressing the transcription factor RORγ”
• Fish Cytokines and Immune Response (2012, background): “It is possible and perhaps likely that expression of the IL-26 gene is induced in an IL-23-dependent manner because IL-23 is known to induce differentiation of Th17 cells, and IL-23 amplifies expression of IL-17 and IL-22 by Th17 cells [214].”
• Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161 (2011, background): “Like LTi cells, these cells are of lymphoid origin, express the IL-7 receptor α-chain (CD127) and the transcription factor RORγt, but they also share with NK cells expression of the activating receptor NKp46 and, in humans, they express the activating receptor NKp44 and the adhesion molecule CD56 (r”
• Intraepithelial type 1 innate lymphoid cells are a unique subset of cytokine responsive interferon-γ-producing cells (2013, positive): “Tonsilar lymphocyte suspensions and peripheral blood mononuclear cells (PBMC) were prepared as previously described (Cella et al., 2009; Cella et al., 2010).”
• CD4+ lymphoid tissue inducer cells promote innate immunity in the gut (2010, background): “Further, a population of NKp46+ ILCs was implicated in promoting innate immunity to C. rodentium (Cella et al., 2009; Satoh-Takayama et al., 2008); however, loss-of-function and gain-of-function experiments were difficult to interpret because of the lack of specific reagents to deplete this cell…”
• Innate Lymphoid Cells: 10 Years On. (2018, neutral): “ILC3s ILC3s are abundant at mucosal sites and are involved in the innate immune response to extracellular bacteria and the containment of intestinal commensals (Cella et al., 2009; Luci et al., 2009; Cupedo et al., 2009; Satoh-Takayama et al., 2008; Buonocore et al., 2010; Sonnenberg et al., 2011, 2”
• Progressive loss of RORγt expression confers distinct functional fates to natural killer cell receptor-expressing RORγt+ innate lymphocytes (2010, neutral): “Genetic lineage tracing revealed that the differentiation of LTi-like cells was characterized by the stable upregulation of NKRs and a progressive loss of RORgt expression.”
• The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells. (2012, neutral): “After birth, IL-22-producing RORgt-dependent ILCs are dominating in mucosal tissues, playing essential roles in innate immunity and wound healing (Cella et al., 2009; Crellin et al., 2010; SatohTakayama et al., 2008; Zenewicz et al., 2008).”