Chen J, Waddell A, Lin Y-D, Cantorna M T
1] Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, Pennsylvania, USA [2] Pathobiology Graduate Program, The Pennsylvania State University, University Park, Pennsylvania, USA.
Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, Pennsylvania, USA.
Mucosal Immunol. 2015 May;8(3):618-26. doi: 10.1038/mi.2014.94. Epub 2014 Oct 15.
Vitamin D receptor (VDR) knockout (KO) mice had fewer Citrobacter rodentium in the feces than wild-type (WT) mice and the kinetics of clearance was faster in VDR KO than WT mice. VDR KO mice had more interleukin-22 (IL-22)-producing innate lymphoid cells (ILCs) and more antibacterial peptides than WT mice. The increased ILCs in the VDR KO mice was a cell-autonomous effect of VDR deficiency on ILC frequencies. Bone marrow (BM) transplantation from VDR KO mice into WT resulted in higher ILCs and colonization resistance of the WT mice. Disruption of the gut microbiota using antibiotics in VDR KO mice reversed colonization resistance to C. rodentium infection. Confirming the role of the microbiota in the colonization resistance of VDR KO mice, transfer of the VDR KO microbiota to WT germ-free mice resulted in colonization resistance. Once colonization resistance was overcome, VDR KO mice had increased susceptibility to C. rodentium. VDR expression is a regulator of ILC frequencies, IL-22, dysbiosis, and C. rodentium susceptibility.
维生素D受体（VDR）基因敲除（KO）小鼠粪便中的鼠柠檬酸杆菌比野生型（WT）小鼠少，且VDR基因敲除小鼠的清除动力学比WT小鼠更快。VDR基因敲除小鼠产生白细胞介素-22（IL-22）的固有淋巴细胞（ILC）和抗菌肽比WT小鼠更多。VDR基因敲除小鼠中ILC的增加是VDR缺乏对ILC频率的细胞自主效应。将VDR基因敲除小鼠的骨髓（BM）移植到WT小鼠中，导致WT小鼠的ILC增加和定植抗性增强。在VDR基因敲除小鼠中使用抗生素破坏肠道微生物群，可逆转对鼠柠檬酸杆菌感染的定植抗性。将VDR基因敲除小鼠的微生物群转移到WT无菌小鼠中导致定植抗性，这证实了微生物群在VDR基因敲除小鼠定植抗性中的作用。一旦克服了定植抗性，VDR基因敲除小鼠对鼠柠檬酸杆菌的易感性就会增加。VDR表达是ILC频率、IL-22、生态失调和对鼠柠檬酸杆菌易感性的调节因子。
