Nicotinic attenuation of central nervous system inflammation and autoimmunity.
The expression of nicotinic acetylcholine receptors by neurons, microglia, and astrocytes suggests possibly diverse mechanisms by which natural nicotinic cholinergic signaling and exposure to nicotine could modulate immune responses within the CNS. In this study, we show that nicotine exposure significantly delays and attenuates inflammatory and autoimmune responses to myelin Ags in the mouse experimental autoimmune encephalomyelitis model. In the periphery, nicotine exposure inhibits the proliferation of autoreactive T cells and alters the cytokine profile of helper T cells. In the CNS, nicotine exposure selectively reduces numbers of CD11c(+) dendritic and CD11b(+) infiltrating monocytes and resident microglial cells and down-regulates the expression of MHC class II, CD80, and CD86 molecules on these cells. The results underscore roles of nicotinic acetylcholine receptors and nicotinic cholinergic signaling in inflammatory and immune responses and suggest novel therapeutic options for the treatment of inflammatory and autoimmune disorders, including those that affect the CNS.
Shi
Fu-Dong
FD
Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA. Fu-Dong.Shi@chw.edu
Piao
Wen-Hua
WH
Kuo
Yen-Ping
YP
Campagnolo
Denise I
DI
Vollmer
Timothy L
TL
Lukas
Ronald J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004673:Encephalomyelitis, Acute Disseminated / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D006023:Glycoproteins / Q000633:toxicity; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018991:Myelin Proteolipid Protein / Q000633:toxicity; D063308:Myelin-Oligodendrocyte Glycoprotein; D009538:Nicotine / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000633:toxicity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006023:Glycoproteins; D007166:Immunosuppressive Agents; D018991:Myelin Proteolipid Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); C435023:myelin proteolipid protein (139-151); D009538:Nicotine