Abstract
Regulatory T cells (Tregs) exert their immunosuppressive activity through several immunoregulatory mechanisms, including the production of anti-inflammatory cytokines such as IL-10. Although several studies suggest a role for Tregs in modulating crescentic GN, the underlying mechanisms are not well understood. Here, using IL-10 reporter mice, we detected IL-10-producing Foxp3(+) T cells in the kidney, blood, and secondary lymphoid tissue in a mouse model of crescentic GN. Specific inactivation of Il10 in Foxp3(+) Tregs eliminated the ability of these cells to suppress renal and systemic production of IFNγ and IL-17; these IL-10-deficient Tregs lost their capacity to attenuate renal tissue injury. These data highlight the suppressive functions of Tregs in crescentic GN and suggest the importance of Treg-derived IL-10 in ameliorating disease severity and in modulating both the Th1 and most notably Th17 immune response.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
B-Lymphocytes / immunology
-
B-Lymphocytes / pathology
-
Blood Proteins / immunology
-
Blood Proteins / toxicity
-
Dendritic Cells / immunology
-
Dendritic Cells / pathology
-
Disease Models, Animal
-
Forkhead Transcription Factors / genetics
-
Glomerulonephritis / chemically induced
-
Glomerulonephritis / immunology*
-
Interleukin-10 / genetics*
-
Interleukin-10 / immunology*
-
Interleukin-10 / metabolism
-
Kidney / immunology
-
Kidney / pathology
-
Macrophages / immunology
-
Macrophages / pathology
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
RNA, Messenger / metabolism
-
Severity of Illness Index
-
Sheep
-
Spleen / immunology
-
T-Lymphocytes, Regulatory / immunology*
-
T-Lymphocytes, Regulatory / pathology*
-
Th1 Cells / immunology
-
Th1 Cells / pathology
-
Th17 Cells / immunology
-
Th17 Cells / pathology
Substances
-
Blood Proteins
-
Forkhead Transcription Factors
-
Foxp3 protein, mouse
-
IL10 protein, mouse
-
RNA, Messenger
-
Interleukin-10