IL-17 signaling-independent central nervous system autoimmunity is negatively regulated by TGF-beta.
Recent studies have established an important role of Th17 in induction of autoimmune diseases. We have found that although IL-17 receptor A (IL-17RA)(-/-) mice were resistant to experimental autoimmune encephalomyelitis, a small number of them developed milder clinical signs of this autoimmune disease. In addition, blockade of TGF-beta in IL-17RA(-/-) mice resulted in much more severe clinical signs of experimental autoimmune encephalomyelitis and significantly increased parenchymal lymphocyte infiltration in the CNS. Furthermore, the number of autoreactive Th1 cells was greatly increased in the inflamed spinal cord of IL-17RA(-/-) mice. These data support a role of IL-17RA-independent mechanisms in causing autoimmunity and its regulation by TGF-beta.
Gonzalez-García
Ines
I
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Zhao
Yani
Y
Ju
Songguang
S
Gu
Qin
Q
Liu
Lin
L
Kolls
Jay K
JK
Lu
Binfeng
B
D000595:Amino Acid Sequence; D000818:Animals; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000502:physiology; D020381:Interleukin-17 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D053722:Receptors, Interleukin-17 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000502:physiology*
D018836:Inflammation Mediators; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D016212:Transforming Growth Factor beta