RORgt and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46⁺ cells

Stephanie L Sanos et al. 2009. Nat Immunol. 10(1):83-91.

Speaker: Yi-Ping Lin (林宜平)                   Time: 13:10~14:00, Jun. 10, 2009

Commentator: Dr. Li-Jin Hsu (徐麗君)    Place: Room 601

The mucosal immune system contains most of the lymphocytes of our body, but we still little known about the function and subtypes of the cells. In addition, the relationship between intestinal epithelium, mucosal lymphocytes and commensal flora to maintain the homeostasis of mucosal immune system is still an interesting issue. In this study, the author found a group of NKp46⁺CD3^- cells that expressed immature NK cells’ cell markers. These mucosal NKp46⁺ cells could separate to different subtypes according to the expression of NK1.1. Depending on the expression level and the developmental requirement of RORgt, these mucosal NKp46⁺ cells could further divide into more different cell subtypes. Compared to spleen NK cells, RORgt^hiNK1.1^intcells has less cytotoxcity and IFN-gproducing. Furthermore, RORgt^hiNK1.1^intcells expressed higher level of IL-22 than other RORgt^neg-int cells or spleen NK cells, instead of IL-17. In germ-free mice, the number of RORgt^hiNK1.1^int cells were more less than normal mice. Besides, the expression of antimicrobial molecules Reg3b and Reg3g were decreased in germ-free mice or IL-22-depleted mice. After recolonization, the numbers of RORgt^hiNK1.1^int cells were increased to normal level and the expression of antimicrobial molecules were the same. In conclusion, mucosal NKp46⁺cells were functionally and phenotypically characterized in this paper. This finding helped us to known the interaction between commensal microflora and mucosal immune system and may provide an potential way to solved some autoimmune disease such as inflammatory bowel disease.

Reference:

1.    David Artis. Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. 2008. Nat. Rev. Immunol. 8: 411-20.

2.    Lauren A Zenewicz et al. Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. 2008. Immunity. 29(6):947-57.