TY - JOUR
T1 - Neural precursor cells inhibit multiple inflammatory signals
AU - Fainstein, Nina
AU - Vaknin, Ilan
AU - Einstein, Ofira
AU - Zisman, Philip
AU - Sasson, S. Z.Ben
AU - Baniyash, Michal
AU - Ben-Hur, Tamir
N1 - Funding Information:
This work was supported by The Israel Science Foundation (grant 140/05) and The Lena P. Harvey Endowment Fund.
PY - 2008/10/29
Y1 - 2008/10/29
N2 - Intravenous neural precursor cell (NPCs) injection attenuates experimental autoimmune encephalomyelitis by reducing autoreactive T cell encephalitogenicity in lymph nodes in vivo. Here we examined NPC-lymphocyte interactions in vitro. NPCs inhibited the induction of T cell activation marker IL-2-Receptor α, ICOS, PD-1 and CTLA-4 and inhibited T cell proliferation. NPCs inhibited T cell activation and proliferation in response to Concavalin-A and to anti-CD3/anti-CD28, which are T cell receptor (TCR)-mediated stimuli, but not in response to phorbol myristate acetate/ionomycin, a TCR-independent stimulus. The suppressive effect was not mediated via downregulation of CD3ε or induction of apoptosis. We next examined NPCs effects on inflammatory-cytokine signaling. NPCs impaired IL-2-mediated phosphorylation of JAK3 in lymphocytes, and inhibited IL-6 mediated proliferation of B9 murine hybridoma cells. In conclusion, NPCs ameliorate TCR-mediated T cell activation and inhibit inflammatory cytokines' signaling in immune cells. These findings may underlie the broad anti-inflammatory effects of NPCs in vivo.
AB - Intravenous neural precursor cell (NPCs) injection attenuates experimental autoimmune encephalomyelitis by reducing autoreactive T cell encephalitogenicity in lymph nodes in vivo. Here we examined NPC-lymphocyte interactions in vitro. NPCs inhibited the induction of T cell activation marker IL-2-Receptor α, ICOS, PD-1 and CTLA-4 and inhibited T cell proliferation. NPCs inhibited T cell activation and proliferation in response to Concavalin-A and to anti-CD3/anti-CD28, which are T cell receptor (TCR)-mediated stimuli, but not in response to phorbol myristate acetate/ionomycin, a TCR-independent stimulus. The suppressive effect was not mediated via downregulation of CD3ε or induction of apoptosis. We next examined NPCs effects on inflammatory-cytokine signaling. NPCs impaired IL-2-mediated phosphorylation of JAK3 in lymphocytes, and inhibited IL-6 mediated proliferation of B9 murine hybridoma cells. In conclusion, NPCs ameliorate TCR-mediated T cell activation and inhibit inflammatory cytokines' signaling in immune cells. These findings may underlie the broad anti-inflammatory effects of NPCs in vivo.
KW - Inflammatory cytokines
KW - Neural precursor cells
KW - T cell
UR - http://www.scopus.com/inward/record.url?scp=53849101373&partnerID=8YFLogxK
U2 - 10.1016/j.mcn.2008.07.007
DO - 10.1016/j.mcn.2008.07.007
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C2 - 18692138
AN - SCOPUS:53849101373
SN - 1044-7431
VL - 39
SP - 335
EP - 341
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 3
ER -
