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However, its multiorgan toxicity needs to be resolved. Dendritic cells (DCs) are the primary target of TP, which induces immunosuppression, and DC\u2010derived exosomes (DEX) can selectively enter DCs in vivo. Here, we encapsulated TP with DEX (DEXTP) to generate TP\u2010targeted delivery to reduce toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The effect of DEXTP was evaluated in murine colitis and RA models. Toxicity was examined by haematoxylin and eosin staining and serum biochemical marker detection. Affinity of DEXs for DCs was tracked by fluorescent labelling. The immune environment was evaluated and mimicked in vitro for further analysis of the mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>DEXTP effectively carried TP to DCs in vivo, and alleviated local inflammation and damage in colitis and RA mice with no obvious toxicity. Additionally, DEXTP reshaped the immune milieu by decreasing CD4<jats:sup>+<\/jats:sup> T\u2010cell levels and increasing regulatory T\u2010cell levels in vivo. Furthermore, consistent T\u2010cell differentiation was observed in vitro, and DC activation was inhibited by alterations in surface factors and secrete cytokines, and by induction of apoptosis or other form of death.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Encapsulating TP with DEX is a new method that both reduces the toxicity of TP and induces immunosuppression in UC and RA mice. The underlying immune mechanism involves DEXTP targeting DCs in vivo, to inhibit DC activation and induce DC apoptosis, which further induces T\u2010cell immunosuppression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15958","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T08:14:05Z","timestamp":1664180045000},"page":"330-346","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Targeted delivery of triptolide by dendritic cell\u2010derived exosomes for colitis and rheumatoid arthritis therapy in murine models"],"prefix":"10.1111","volume":"180","author":[{"given":"Quan","family":"Rao","sequence":"first","affiliation":[{"name":"Department of General Surgery, Beijing Friendship Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangchao","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Friendship Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Friendship Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Friendship Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Beijing Friendship Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Friendship Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7063-2474","authenticated-orcid":false,"given":"Zhijie","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Friendship Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luqi","family":"Huang","sequence":"additional","affiliation":[{"name":"Resource Center for Chinese Materia Medica China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,25]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1807"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.5.3522"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-03-0854"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2018.01.006"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0NR07622H"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3978"},{"issue":"1","key":"e_1_2_13_8_1","first-page":"89","article-title":"Mice lacking cannabinoid CB1\u2010, CB2\u2010receptors or both receptors show increased susceptibility to trinitrobenzene sulfonic acid (TNBS)\u2010induced colitis","volume":"61","author":"Engel M. 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