Intestinal Lin(-)c-Kit(+)NKp46(-)CD4(-) Population Strongly Produces IL-22 upon IL-1 beta Stimulation
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SCOPUS
- Title
- Intestinal Lin(-)c-Kit(+)NKp46(-)CD4(-) Population Strongly Produces IL-22 upon IL-1 beta Stimulation
- Authors
- Lee, Y; Kumagai, Y; Jang, MS; Kim, JH; Yang, BG; Lee, EJ; Kim, YM; Akira, S; Jang, MH
- Date Issued
- 2013-05-15
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- 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-1 beta, IL-23, or IL-1 beta and IL-23 stimulation. In addition, we showed that the majority of the Lin(-)c-Kit(+)NKp46(-)CD4(-) population was IL-7R alpha(+)CD34(-)beta 7(int) cells, and IL-7R alpha(-) cells could be divided into three subsets (CD34(+)beta 7(int), CD34(-)beta 7(int), and CD34(int)beta 7(hi) cells). The IL-7R alpha(+)CD34(-)beta 7(int) cells strongly expressed the transcripts for Il17f and Il22 after costimulation with IL-1 beta and IL-23. The IL-7R alpha(-)CD34(+)beta 7(int) and IL-7R alpha(-)CD34(int)beta 7(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-7R alpha(-)CD34(+)beta 7(int) cells highly expressed alpha-defensins and showed no differentiation. Taken together, these findings indicate that the IL-7R alpha(-)CD34(+)beta 7(int) and IL-7R alpha(-)CD34(int)beta 7(hi) populations are mast cell progenitors, and the IL-7R alpha(-)CD34(-)beta 7(int) (CD4(-) LTi-like cells) and IL-7R alpha(-)CD34(-)beta 7(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 alpha-defensins, respectively.
- Keywords
- INNATE LYMPHOID-CELLS; INFLAMMATORY-BOWEL-DISEASE; MAST-CELLS; ANTIMICROBIAL PEPTIDES; ALPHA-DEFENSINS; HOST-DEFENSE; BONE-MARROW; TRICHINELLA-SPIRALIS; BARRIER FUNCTION; DENDRITIC CELLS
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/13665
- DOI
- 10.4049/JIMMUNOL.1201452
- ISSN
- 0022-1767
- Article Type
- Article
- Citation
- JOURNAL OF IMMUNOLOGY, vol. 190, no. 10, page. 5296 - 5305, 2013-05-15
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