Suppression of allograft rejection by regulatory B cells induced via TLR signaling
B lymphocytes have long been recognized for their critical contributions to adaptive immunity, providing defense against pathogens through cognate antigen presentation to T cells and Ab production. More recently appreciated is that B cells are also integral in securing self-tolerance; this has led t...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2022-09-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.152213 |
| _version_ | 1827768070232342528 |
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| author | Kang Mi Lee Qiang Fu Guoli Huai Kevin Deng Ji Lei Lisa Kojima Divyansh Agarwal Peter van Galen Shoko Kimura Naoki Tanimine Laura Washburn Heidi Yeh Ali Naji Charles G. Rickert Christian LeGuern James F. Markmann |
| author_facet | Kang Mi Lee Qiang Fu Guoli Huai Kevin Deng Ji Lei Lisa Kojima Divyansh Agarwal Peter van Galen Shoko Kimura Naoki Tanimine Laura Washburn Heidi Yeh Ali Naji Charles G. Rickert Christian LeGuern James F. Markmann |
| author_sort | Kang Mi Lee |
| collection | DOAJ |
| description | B lymphocytes have long been recognized for their critical contributions to adaptive immunity, providing defense against pathogens through cognate antigen presentation to T cells and Ab production. More recently appreciated is that B cells are also integral in securing self-tolerance; this has led to interest in their therapeutic application to downregulate unwanted immune responses, such as transplant rejection. In this study, we found that PMA- and ionomycin-activated mouse B cells acquire regulatory properties following stimulation through TLR4/TLR9 receptors (Bregs-TLR). Bregs-TLR efficiently inhibited T cell proliferation in vitro and prevented allograft rejection. Unlike most reported Breg activities, the inhibition of alloimmune responses by Bregs-TLR relied on the expression of TGF-β and not IL-10. In vivo, Bregs-TLR interrupted donor-specific T cell expansion and induced Tregs in a TGF-β–dependent manner. RNA-Seq analyses corroborated the involvement of TGF-β pathways in Breg-TLR function, identified potential gene pathways implicated in preventing graft rejection, and suggested targets to foster Breg regulation. |
| first_indexed | 2024-03-11T12:08:10Z |
| format | Article |
| id | doaj.art-d2f9ca1c1ef9466fa9f360467b2f90da |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:08:10Z |
| publishDate | 2022-09-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-d2f9ca1c1ef9466fa9f360467b2f90da2023-11-07T16:24:32ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-09-01717Suppression of allograft rejection by regulatory B cells induced via TLR signalingKang Mi LeeQiang FuGuoli HuaiKevin DengJi LeiLisa KojimaDivyansh AgarwalPeter van GalenShoko KimuraNaoki TanimineLaura WashburnHeidi YehAli NajiCharles G. RickertChristian LeGuernJames F. MarkmannB lymphocytes have long been recognized for their critical contributions to adaptive immunity, providing defense against pathogens through cognate antigen presentation to T cells and Ab production. More recently appreciated is that B cells are also integral in securing self-tolerance; this has led to interest in their therapeutic application to downregulate unwanted immune responses, such as transplant rejection. In this study, we found that PMA- and ionomycin-activated mouse B cells acquire regulatory properties following stimulation through TLR4/TLR9 receptors (Bregs-TLR). Bregs-TLR efficiently inhibited T cell proliferation in vitro and prevented allograft rejection. Unlike most reported Breg activities, the inhibition of alloimmune responses by Bregs-TLR relied on the expression of TGF-β and not IL-10. In vivo, Bregs-TLR interrupted donor-specific T cell expansion and induced Tregs in a TGF-β–dependent manner. RNA-Seq analyses corroborated the involvement of TGF-β pathways in Breg-TLR function, identified potential gene pathways implicated in preventing graft rejection, and suggested targets to foster Breg regulation.https://doi.org/10.1172/jci.insight.152213ImmunologyTransplantation |
| spellingShingle | Kang Mi Lee Qiang Fu Guoli Huai Kevin Deng Ji Lei Lisa Kojima Divyansh Agarwal Peter van Galen Shoko Kimura Naoki Tanimine Laura Washburn Heidi Yeh Ali Naji Charles G. Rickert Christian LeGuern James F. Markmann Suppression of allograft rejection by regulatory B cells induced via TLR signaling JCI Insight Immunology Transplantation |
| title | Suppression of allograft rejection by regulatory B cells induced via TLR signaling |
| title_full | Suppression of allograft rejection by regulatory B cells induced via TLR signaling |
| title_fullStr | Suppression of allograft rejection by regulatory B cells induced via TLR signaling |
| title_full_unstemmed | Suppression of allograft rejection by regulatory B cells induced via TLR signaling |
| title_short | Suppression of allograft rejection by regulatory B cells induced via TLR signaling |
| title_sort | suppression of allograft rejection by regulatory b cells induced via tlr signaling |
| topic | Immunology Transplantation |
| url | https://doi.org/10.1172/jci.insight.152213 |
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