DC Field | Value | Language |
---|---|---|
dc.contributor.author | Zhao, Jing | ko |
dc.contributor.author | Jung, Sungwook | ko |
dc.contributor.author | Li, Xiaofei | ko |
dc.contributor.author | Li, Lushen | ko |
dc.contributor.author | Kasinath, Vivek | ko |
dc.contributor.author | Zhang, Hengcheng | ko |
dc.contributor.author | Movahedi, Said N. | ko |
dc.contributor.author | Mardini, Ahmad | ko |
dc.contributor.author | Sabiu, Gianmarco | ko |
dc.contributor.author | Hwang, Yoonha | ko |
dc.contributor.author | Saxena, Vikas | ko |
dc.contributor.author | Song, Yang | ko |
dc.contributor.author | Ma, Bing | ko |
dc.contributor.author | Acton, Sophie E. | ko |
dc.contributor.author | Kim, Pilhan | ko |
dc.contributor.author | Madsen, Joren C. | ko |
dc.contributor.author | Sage, Peter T. | ko |
dc.contributor.author | Tullius, Stefan G. | ko |
dc.contributor.author | Tsokos, George C. | ko |
dc.contributor.author | Bromberg, Jonathan S. | ko |
dc.contributor.author | Abdi, Reza | ko |
dc.date.accessioned | 2023-01-28T03:01:56Z | - |
dc.date.available | 2023-01-28T03:01:56Z | - |
dc.date.created | 2023-01-28 | - |
dc.date.created | 2023-01-28 | - |
dc.date.created | 2023-01-28 | - |
dc.date.issued | 2022-12 | - |
dc.identifier.citation | JOURNAL OF CLINICAL INVESTIGATION, v.132, no.24 | - |
dc.identifier.issn | 0021-9738 | - |
dc.identifier.uri | http://hdl.handle.net/10203/304767 | - |
dc.description.abstract | The lymph node (LN) is the primary site of alloimmunity activation and regulation during transplantation. Here, we investigated how fibroblastic reticular cells (FRCs) facilitate the tolerance induced by anti-CD40L in a murine model of heart transplantation. We found that both the absence of LNs and FRC depletion abrogated the effect of anti-CD40L in prolonging murine heart allograft survival. Depletion of FRCs impaired homing of T cells across the high endothelial venules (HEVs) and promoted formation of alloreactive T cells in the LNs in heart-transplanted mice treated with anti-CD40L. Single-cell RNA sequencing of the LNs showed that anti-CD40L promotes a Madcam1+ FRC subset. FRCs also promoted the formation of regulatory T cells (Tregs) in vitro. Nanoparticles (NPs) containing anti-CD40L were selectively delivered to the LNs by coating them with MECA-79, which binds to peripheral node addressin (PNAd) glycoproteins expressed exclusively by HEVs. Treatment with these MECA-79-anti-CD40L-NPs markedly delayed the onset of heart allograft rejection and increased the presence of Tregs. Finally, combined MECA-79-anti-CD40L-NPs and rapamycin treatment resulted in markedly longer allograft survival than soluble anti-CD40L and rapamycin. These data demonstrate that FRCs are critical to facilitating costimulatory blockade. LN-targeted nanodelivery of anti-CD40L could effectively promote heart allograft acceptance. | - |
dc.language | English | - |
dc.publisher | AMER SOC CLINICAL INVESTIGATION INC | - |
dc.title | Delivery of costimulatory blockade to lymph nodes promotes transplant acceptance in mice | - |
dc.type | Article | - |
dc.identifier.wosid | 000905494000006 | - |
dc.identifier.scopusid | 2-s2.0-85144538818 | - |
dc.type.rims | ART | - |
dc.citation.volume | 132 | - |
dc.citation.issue | 24 | - |
dc.citation.publicationname | JOURNAL OF CLINICAL INVESTIGATION | - |
dc.identifier.doi | 10.1172/JCI159672 | - |
dc.contributor.localauthor | Kim, Pilhan | - |
dc.contributor.nonIdAuthor | Zhao, Jing | - |
dc.contributor.nonIdAuthor | Jung, Sungwook | - |
dc.contributor.nonIdAuthor | Li, Xiaofei | - |
dc.contributor.nonIdAuthor | Li, Lushen | - |
dc.contributor.nonIdAuthor | Kasinath, Vivek | - |
dc.contributor.nonIdAuthor | Zhang, Hengcheng | - |
dc.contributor.nonIdAuthor | Movahedi, Said N. | - |
dc.contributor.nonIdAuthor | Mardini, Ahmad | - |
dc.contributor.nonIdAuthor | Sabiu, Gianmarco | - |
dc.contributor.nonIdAuthor | Hwang, Yoonha | - |
dc.contributor.nonIdAuthor | Saxena, Vikas | - |
dc.contributor.nonIdAuthor | Song, Yang | - |
dc.contributor.nonIdAuthor | Ma, Bing | - |
dc.contributor.nonIdAuthor | Acton, Sophie E. | - |
dc.contributor.nonIdAuthor | Madsen, Joren C. | - |
dc.contributor.nonIdAuthor | Sage, Peter T. | - |
dc.contributor.nonIdAuthor | Tullius, Stefan G. | - |
dc.contributor.nonIdAuthor | Tsokos, George C. | - |
dc.contributor.nonIdAuthor | Bromberg, Jonathan S. | - |
dc.contributor.nonIdAuthor | Abdi, Reza | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | FIBROBLASTIC RETICULAR CELLS | - |
dc.subject.keywordPlus | REGULATORY T-CELLS | - |
dc.subject.keywordPlus | HIGH ENDOTHELIAL VENULES | - |
dc.subject.keywordPlus | DENDRITIC CELLS | - |
dc.subject.keywordPlus | L-SELECTIN | - |
dc.subject.keywordPlus | CARDIOVASCULAR-DISEASE | - |
dc.subject.keywordPlus | VASCULAR ADDRESSIN | - |
dc.subject.keywordPlus | IMMUNE-RESPONSE | - |
dc.subject.keywordPlus | IN-VITRO | - |
dc.subject.keywordPlus | DRUG | - |
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