an early reduction in treg cells correlates with enhanced local inflammation in cutaneous leishmaniasis in ccr6-deficient mice早期减少treg细胞与增强炎症在ccr6-deficient小鼠皮肤利什曼病.pdfVIP

An Early Reduction in Treg Cells Correlates with Enhanced Local Inflammation in Cutaneous Leishmaniasis in CCR6-Deficient Mice 1 1 1,2 1 1 Thomas Barth , Dominic Schmidt , Catherine Botteron , Trang T. T. Nguyen , Uwe Ritter , ¨ 1 1 Daniela N. Mannel , Anja Lechner * 1 Institute of Immunology, University of Regensburg, Regensburg, Germany, 2 Institute of Pediatrics, University of Regensburg, Regensburg, Germany Abstract Resistance to Leishmania major infection is dependent on the development of a cell-mediated Th1 immune response in resistant C57BL/6 mice whereas Th2-prone BALB/c mice develop non-healing lesions after infection. The chemokine receptor CCR6 is shared by anti-inflammatory regulatory T cells and pro-inflammatory Th17 cells. In a recent study we showed that C57BL/6 mice deficient in CCR6 exhibited enhanced footpad swelling and impaired T helper cell migration indicated by reduced recruitment of total T helper cells into the skin after infection and a reduced delayed type hypersensitivity reaction. Based on these findings we tested whether the lack of CCR6 alters Treg or Th17 cell responses during the course of Leishmania major infection. When we analyzed T cell subsets in the lymph nodes of CCR6-deficient mice, Th17 cell numbers were not different. However, reduced numbers of Treg cells paralleled with a stronger IFNc response. Furthermore, the early increase in IFNc-producing cells correlated with increased local tissue inflammation at later time points. Our data indicate an important role of CCR6 for Treg cells and a redundant role for Th17 cells in a Th1 cell