| 研究概要 |
Small intestinal innate lymphoid cells (ILCs) regulate intestinal epithelial cell homeostasis and help to prevent pathogenic bacterial infections by producing IL-22. In a microarray 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, mast cell proteases, and Rorc. We then subdivided the Lin-c-Kit+Sca-1- cells into three groups―Lin-c-Kit+NKp46-CD4-, CD4+ LTi-like cells, and 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. We also showed that the majority of the Lin-c-Kit+NKp46-CD4- population was IL-7R+CD34-β7int cells, and IL-7R- cells could be divided into three subsets (CD34+β7int, CD34-β7int, and CD34intβ7hi cells). The IL-7R+CD34-β7int cells strongly expressed the transcripts for Il17f and Il22 after costimulation with IL-1β and IL-23. The IL-7R-CD34+β7int and IL-7R-CD34intβ7hi cells differentiated almost entirely into mast cells, whereas the IL-7R-CD34-β7int cells highly expressed a-defensins and showed no differentiation. Taken together, these findings indicate that the IL-7R-CD34+β7int and IL-7R-CD34intβ7hi populations are mast cell progenitors, and the IL-7R+CD34-β7int (CD4- LTi-like cells) and IL-7R-CD34-β7int 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.
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