Publication Date:
2013-05-04
Description:
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.
Print ISSN:
0022-1767
Electronic ISSN:
1550-6606
Topics:
Medicine
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