Regional neural activation defines a gateway for autoreactive T cells to cross the blood-brain barrier.
Although it is believed that neural activation can affect immune responses, very little is known about the neuroimmune interactions involved, especially the regulators of immune traffic across the blood-brain barrier which occurs in neuroimmune diseases such as multiple sclerosis (MS). Using a mouse model of MS, experimental autoimmune encephalomyelitis, we show that autoreactive T cells access the central nervous system via the fifth lumbar spinal cord. This location is defined by IL-6 amplifier-dependent upregulation of the chemokine CCL20 in associated dorsal blood vessels, which in turn depends on gravity-induced activation of sensory neurons by the soleus muscle in the leg. Impairing soleus muscle contraction by tail suspension is sufficient to reduce localized chemokine expression and block entry of pathogenic T cells at the fifth lumbar cord, suggesting that regional neuroimmune interactions may offer therapeutic targets for a variety of neurological diseases.
Laboratory of Developmental Immunology, JST-CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine, and WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
Yasunobu
Y
Arima
Masaya
M
Harada
Daisuke
D
Kamimura
Jin-Haeng
JH
Park
Fuminori
F
Kawano
Fiona E
FE
Yull
Tadafumi
T
Kawamoto
Yoichiro
Y
Iwakura
Ulrich A K
UA
Betz
Gabriel
G
Márquez
Timothy S
TS
Blackwell
Yoshinobu
Y
Ohira
Toshio
T
Hirano
Masaaki
M
Murakami
D000818:Animals; D001812:Blood-Brain Barrier; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D002465:Cell Movement; D054418:Chemokine CCL20 / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D006112:Gravitation; D015850:Interleukin-6 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology; D018482:Muscle, Skeletal / Q000294:innervation; D015213:Neuroimmunomodulation; D013116:Spinal Cord / Q000098:blood supply
D054418:Chemokine CCL20; D015850:Interleukin-6