The sympathetic nervous system modulates CD4(+)FoxP3(+) regulatory T cells via a TGF-beta-dependent mechanism.
CD4(+)FoxP3(+) Tregs are essential mediators of the peripheral immune response to self-antigens. Accordingly, the homeostatic regulation of Treg activity and number would impact on the immune response to both self- and non-self antigens. Because the sympathetic nervous system (SNS) interacts chemically and physically with the central and peripheral immune system and exerts a direct influence on antigen-presenting cells and effector lymphocytes, we have investigated the effect of chemical ablation of the SNS on the number and function of peripheral Treg. Removal of murine peripheral sympathetic innervation by 6-hydroxydopamine induced an increase in splenic and lymph node CD4(+)FoxP3(+) Tregs by a TGF-beta-dependent mechanism. Further, this increase in Tregs coincides with an inhibition of the induction of experimental autoimmune encephalomyelitis. Our results demonstrate that the SNS is an important contributor to the maintenance of peripheral Treg and TGF-beta acts as a bridge between the immune system and the nervous system. Neurological events mediated by the SNS, such as a stress response, may affect the number of T cells that regulate an immune response. Additionally, targeting Tregs via the SNS may be a novel approach to the prevention or treatment of autoimmune diseases.
Bhowmick
Sourojit
S
Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
Singh
Anurag
A
Flavell
Richard A
RA
Clark
Robert B
RB
O'Rourke
James
J
Cone
Robert E
RE
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology* / Q000294:innervation; D051379:Mice; D018345:Mice, Knockout; D016627:Oxidopamine / Q000009:adverse effects / Q000494:pharmacology; D013154:Spleen / Q000276:immunology* / Q000294:innervation; D013312:Stress, Physiological / Q000276:immunology; D013564:Sympathetic Nervous System / Q000276:immunology*; D013565:Sympatholytics / Q000009:adverse effects / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology*
D013565:Sympatholytics; D016212:Transforming Growth Factor beta; D016627:Oxidopamine