title: Intestinal Lin- c-Kit+ NKp46- CD4- population strongly produces IL-22 upon IL-1β stimulation.
abstract: Small intestinal innate lymphoid cells (ILCs) regulate intestinal epithelial cell homeostasis and help to prevent pathogenic bacterial infections by producing IL-22. In a global gene-expression analysis comparing small intestinal ILCs (Lin(-)c-Kit(+)Sca-1(-) cells) with non-ILCs (Lin(-)c-Kit(-)Sca-1(-) cells), we found that Lin(-)c-Kit(+)Sca-1(-) cells highly expressed the mRNAs for Il22, antimicrobial peptides, Csf2rb2 (Il3r), mast cell proteases, and Rorc. We then subdivided the Lin(-)c-Kit(+)Sca-1(-) cells into three groups--Lin(-)c-Kit(+)NKp46(-)CD4(-), Lin(-)c-Kit(+)NKp46(-)CD4(+) (CD4(+) LTi-like cells), and Lin(-)c-Kit(+)NKp46(+) (NKp46(+) ILC22 cells)--and showed that the Lin(-)c-Kit(+)NKp46(-)CD4(-) cells produced the highest level of IL-22 protein after IL-1β, IL-23, or IL-1β and IL-23 stimulation. In addition, we showed that the majority of the Lin(-)c-Kit(+)NKp46(-)CD4(-) population was IL-7Rα(+)CD34(-)β7(int) cells, and IL-7Rα(-) cells could be divided into three subsets (CD34(+)β7(int), CD34(-)β7(int), and CD34(int)β7(hi) cells). The IL-7Rα(+)CD34(-)β7(int) cells strongly expressed the transcripts for Il17f and Il22 after costimulation with IL-1β and IL-23. The IL-7Rα(-)CD34(+)β7(int) and IL-7Rα(-)CD34(int)β7(hi) cells predominantly expressed the transcripts for mast cell proteases and differentiated almost entirely into mast cells after 1 wk in culture medium supplemented with a cytokine mixture, whereas the IL-7Rα(-)CD34(-)β7(int) cells highly expressed α-defensins and showed no differentiation. Taken together, these findings indicate that the IL-7Rα(-)CD34(+)β7(int) and IL-7Rα(-)CD34(int)β7(hi) populations are mast cell progenitors, and the IL-7Rα(+)CD34(-)β7(int) (CD4(-) LTi-like cells) and IL-7Rα(-)CD34(-)β7(int) populations within Lin(-)c-Kit(+)NKp46(-)CD4(-) cells may control intestinal homeostasis and provide intestinal protection by producing high levels of IL-22 and α-defensins, respectively.
authors.affiliation: Laboratory of Gastrointestinal Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan. yalee77@ifrec.osaka-u.ac.jp
authors.forename: Youngae
authors.initials: Y
authors.lastname: Lee
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Kumagai
authors.forename: Min Seong
authors.initials: MS
authors.lastname: Jang
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Bo-Gie
authors.initials: BG
authors.lastname: Yang
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Lee
authors.forename: You-Me
authors.initials: YM
authors.lastname: Kim
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Myoung Ho
authors.initials: MH
authors.lastname: Jang
mesh_terms: D000818:Animals; D018952:Antigens, CD34; D000950:Antigens, Ly / Q000378:metabolism; D001424:Bacterial Infections / Q000276:immunology* / Q000517:prevention & control; D015704:CD4 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D053583:Interleukin-1beta / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D007378:Interleukins / Q000096:biosynthesis* / Q000276:immunology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D020395:Receptors, Interleukin-7; D023084:alpha-Defensins / Q000096:biosynthesis / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D018952:Antigens, CD34; D000950:Antigens, Ly; D015704:CD4 Antigens; D053583:Interleukin-1beta; D053759:Interleukin-23; D053699:Interleukin-7 Receptor alpha Subunit; D007378:Interleukins; D055627:Natural Cytotoxicity Triggering Receptor 1; D019009:Proto-Oncogene Proteins c-kit; D020395:Receptors, Interleukin-7; D023084:alpha-Defensins; D000097043:Interleukin-22; C118384:Ncr1 protein, mouse; C415350:interleukin-7 receptor, alpha chain