Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells.
IL-17 and IL-22 are typical cytokines produced by the Th17 T cell subset, but it is unclear if Th17 cytokines can be produced by other cell types. We demonstrate that IL-10-deficient and IL-10R-deficient macrophages stimulated with lipopolysaccharide produce high levels of IL-17 and IL-22. Addition of exogenous IL-10 to IL-10-deficient macrophages abolished IL-17 production. When IL-10-deficient and IL-10R-deficient splenocytes were cultured under Th17 polarizing conditions, the population of IL-17-producing cells was increased and the cultures produced significantly higher levels of IL-17 and IL-22. The addition of recombinant IL-10 to IL-10-deficient splenocytes significantly decreased the percentage of IL-17-producing CD4(+) T cells. Finally, the mRNA for the Th17 transcription factor retinoic acid-related orphan receptor (ROR)gammat was significantly elevated in IL-10-deficient spleen cells and macrophages. These data demonstrate that Th17 cytokines and RORgammat are also expressed in macrophages and that IL-10 negatively regulates the expression of Th17 cytokines and RORgammat by both macrophages and T cells.
Immunology Institute, Mount Sinai School of Medicine, New York, NY, USA.
Yongpeng
Y
Gu
Jianfei
J
Yang
Xinshou
X
Ouyang
Weicheng
W
Liu
Hongxing
H
Li
Jianjun
J
Yang
Jonathan
J
Bromberg
Shu-Hsia
SH
Chen
Lloyd
L
Mayer
Jay C
JC
Unkeless
Huabao
H
Xiong
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D053701:Receptors, Interleukin-10 / Q000172:deficiency / Q000276:immunology / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000276:immunology / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D000097043:Interleukin-22
D016753:Interleukin-10; D020381:Interleukin-17; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D053701:Receptors, Interleukin-10; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D000097043:Interleukin-22; C539901:Rorc protein, mouse