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It is shown that exosomes may act as signal conveyors for nanoparticle\u2010induced systemic immune responses. Exosomes are extracellularly secreted membrane vesicles which act as Trojan horses for the dissemination and intercellular communication of natural nanosized particles (like viruses). Upon exposure to magnetic iron oxide nanoparticles (MIONs), it is possible to dose\u2010dependently generate a significant number of exosomes in the alveolar region of BALB\/c mice. These exosomes are quickly eliminated from alveoli into systemic circulation and largely transfer their signals to the immune system. Maturation of dendritic cells and activation of splenic T cells are significantly induced by these exosomes. Furthermore, exosome\u2010induced T\u2010cell activation is more efficient toward sensitized T cells and in ovalbumin (OVA)\u2010sensitized mice than in the unsensitized counterparts. Activation of systemic T cells reveals a T helper 1 polarization and aggravated inflammation, which poses potential hazards to the deterioration of allergic diseases in OVA\u2010sensitized mice. The studies suggest that exosomes may act as conveyors for extrapulmonary signal transduction in nanoparticle\u2010induced immune systemic responses, which are the key in vivo processes of manufactured nanoparticles executing either biomedical functions or toxic responses.<\/jats:p>","DOI":"10.1002\/smll.201101708","type":"journal-article","created":{"date-parts":[[2011,12,6]],"date-time":"2011-12-06T07:36:04Z","timestamp":1323156964000},"page":"404-412","source":"Crossref","is-referenced-by-count":95,"title":["Exosomes as Extrapulmonary Signaling Conveyors for Nanoparticle\u2010Induced Systemic Immune Activation"],"prefix":"10.1002","volume":"8","author":[{"given":"Motao","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiye","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyue","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangjun","family":"Nie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,12,6]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.010909.105819"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nnano.2007.223"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/nl103432w"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/nl801828z"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nnano.2009.151"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nnano.2009.175"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/nl0723634"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfj027"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308413101"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-05-158642"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2567"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1831413100"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nnano.2008.30"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja074936k"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni0305-223"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.9306"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2009.04.003"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200701-036OC"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2008-0276OC"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.7939"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.03.00041703"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-3-10"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-3-9"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-01-0220"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-153536"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200535615"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni854"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-006-0102-0"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/mp049907k"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2006.05.016"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(98)00256-4"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0598-594"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.59.061506.154139"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2007.01600.x"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5155"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7631"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2006.01288.x"},{"key":"e_1_2_7_38_2","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.4049\/jimmunol.143.9.2887","volume":"143","author":"Fong T. 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