Abstract
The homing of dendritic cells and T cells to secondary lymphoid organs requires chemokine receptor 7 (CCR7) expression on these cells. T cells mediate the pathogenesis of experimental accelerated nephrotoxic serum nephritis (NTS), including its suppression by regulatory T cells (Tregs), but the contribution of CCR7 to this disease is unknown. Here, we compared the development of NTS in CCR7-knockout (KO) and wild-type (WT) mice. Compared with WT mice, CCR7KO mice developed more severe disease with significantly more inflammatory cells infiltrating the kidney. These cells included FoxP3(+) Tregs, which were virtually absent from WT kidneys. The adoptive transfer of WT Tregs into CCR7KO mice at the time of immunization protected the recipients from disease; these cells homed to secondary lymphoid organs but not to kidneys. Conversely, adoptive transfer of CCR7KO Tregs into WT mice did not inhibit development of NTS. These data suggest that NTS can develop without CCR7 expression, but Treg-mediated disease suppression, which seems to occur in secondary lymphoid organs, requires CCR7.
| Original language | English |
|---|---|
| Pages (from-to) | 42-52 |
| Number of pages | 11 |
| Journal | Journal of the American Society of Nephrology : JASN |
| Volume | 21 |
| Issue number | 1 |
| Early online date | 16 Nov 2009 |
| DOIs | |
| Publication status | Published - 1 Jan 2010 |
Keywords
- Acute Disease
- Animals
- Cell Movement
- Cytokines
- Disease Models, Animal
- Down-Regulation
- Immune System
- Kidney
- Lymph Nodes
- Mice
- Mice, Inbred BALB C
- Mice, Knockout
- Nephritis
- Receptors, CCR7
- Severity of Illness Index
- T-Lymphocytes, Regulatory