PMID- 20534450 OWN - NLM STAT- MEDLINE DCOM- 20100714 LR - 20231213 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 107 IP - 24 DP - 2010 Jun 15 TI - Expansion of human NK-22 cells with IL-7, IL-2, and IL-1beta reveals intrinsic functional plasticity. PG - 10961-6 LID - 10.1073/pnas.1005641107 [doi] AB - Natural killer-22 (NK-22) cells are a human NK cell subset situated in mucosal-associated lymphoid tissues that specialize in IL-22 secretion in response to IL-23. Here we investigated the cytokine requirements for NK-22 cell expansion. IL-7 maintained the survival of NK-22 cells and IL-22 production in response to IL-23 but was insufficient to induce robust expansion. Proliferation of NK-22 cells was increased markedly by adding either IL-1beta or IL-2 to IL-7 and was even stronger in the presence of IL-1beta plus IL-2. In contrast to IL-7, continuous culture in IL-1beta and IL-2 modified NK-22 cytokine profiles. IL-1beta promoted constitutive IL-22 secretion rather than acute IL-22 production in response to IL-23 and induced IL-17 in some cells. IL-2 reduced secretion of IL-22 and IL-17, increasing production of IFN-gamma and leukemia inhibitory factor. Functional deviation toward IFN-gamma production also was induced by continuous culture in IL-23. These results demonstrate the functional plasticity of NK-22 cells, which may allow flexible responses to different pathogens. Finally, we found that NK-22 cells released the B-cell survival factor, B-cell activating factor belonging to the TNF family (BAFF), suggesting a potential role of NK-22 cells in promoting B-cell-mediated mucosal immunity. FAU - Cella, Marina AU - Cella M AD - Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA. FAU - Otero, Karel AU - Otero K FAU - Colonna, Marco AU - Colonna M LA - eng GR - P30 DK056341/DK/NIDDK NIH HHS/United States GR - P30 DK056341-10/DK/NIDDK NIH HHS/United States GR - A1067854/PHS HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20100601 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (B-Cell Activating Factor) RN - 0 (Cytokines) RN - 0 (DNA Primers) RN - 0 (IL2 protein, human) RN - 0 (IL23A protein, human) RN - 0 (IL7 protein, human) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-2) RN - 0 (Interleukin-23 Subunit p19) RN - 0 (Interleukin-7) RN - 0 (Interleukins) RN - 0 (LIF protein, human) RN - 0 (Leukemia Inhibitory Factor) RN - 0 (RNA, Messenger) RN - 0 (Recombinant Proteins) RN - 0 (TNFSF13B protein, human) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - B-Cell Activating Factor/biosynthesis MH - Base Sequence MH - Cell Proliferation/drug effects MH - Cytokines/biosynthesis/genetics MH - DNA Primers/genetics MH - Humans MH - In Vitro Techniques MH - Interferon-gamma/biosynthesis MH - Interleukin-1beta/*pharmacology MH - Interleukin-2/*pharmacology MH - Interleukin-23 Subunit p19/pharmacology MH - Interleukin-7/*pharmacology MH - Interleukins/*biosynthesis MH - Killer Cells, Natural/*classification/cytology/drug effects/*immunology MH - Leukemia Inhibitory Factor/biosynthesis MH - Lymphocyte Subsets/*classification/cytology/drug effects/*immunology MH - Palatine Tonsil/cytology/immunology MH - RNA, Messenger/genetics/metabolism MH - Recombinant Proteins/pharmacology MH - Interleukin-22 PMC - PMC2890739 COIS- The authors declare no conflict of interest. EDAT- 2010/06/11 06:00 MHDA- 2010/07/16 06:00 PMCR- 2010/06/01 CRDT- 2010/06/11 06:00 PHST- 2010/06/11 06:00 [entrez] PHST- 2010/06/11 06:00 [pubmed] PHST- 2010/07/16 06:00 [medline] PHST- 2010/06/01 00:00 [pmc-release] AID - 1005641107 [pii] AID - 201005641 [pii] AID - 10.1073/pnas.1005641107 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):10961-6. doi: 10.1073/pnas.1005641107. Epub 2010 Jun 1.