Autoantigen presentation by splenic dendritic cells is required for RBC-specific autoimmunity.
Autoantigen presentation by splenic dendritic cells is required for RBC-specific autoimmunity.
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DOI：
10.1111/trf.16191
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发表时间：
2021-01
期刊：
影响因子：
2.9
通讯作者：
Hudson, Krystalyn E.
中科院分区：
文献类型：
--
作者：
Richards, Amanda L.;Qiu, Annie;Dei Zotti, Flavia;Sheldon, Kathryn;Usaneerungrueng, Chomkan;Gruber, David R.;Hudson, Krystalyn E.
Failure of humoral tolerance to red blood cell (RBC) antigens may lead to autoimmune hemolytic anemia (AIHA), a severe and sometimes fatal, disease. Previous studies have shown that although tolerance is robust in HOD mice, autoantibodies are generated upon adoptive transfer of OTII CD4+ T cells, which are specific for an epitope contained within the HOD antigen. These data imply that antigen presenting cells (APCs) are presenting RBC-derived autoantigen(s) and are capable of driving T cell activation. Given that multiple APCs participate in erythrophagocytosis, we utilized a transgenic approach to determine which cellular subsets were required for autoantigen presentation and subsequent autoreactive T cell activation. HOD mice, which express an RBC-specific antigen consisting of hen egg lysozyme, ovalbumin, and human blood group molecule Duffy, were bred with IAbfl/fl and Cre-expressing transgenic animals to generate mice that lack I-Ab expression on particular cell subsets. OTII CD4+ T cell proliferation was assessed in vivo in HOD+I-Abfl/flxCre+ mice and in vitro upon co-culture with sorted APCs. Analysis of HOD+I-Abfl/flxCre+ mice demonstrated that splenic conventional DCs, but not macrophages or monocytes, were required for autoantigen presentation to OTII CD4+ T cells. Subsequent in vitro co-culture experiments revealed that both CD8+ and CD8− dendritic cell (DC) subsets participate in erythrophagocytosis, present RBC-derived autoantigen, and stimulate autoreactive T cell proliferation. These data suggest that if erythrocyte T cell tolerance fails, DCs are capable of initiating autoimmune responses. As such, targeting DCs may be a fruitful strategy for AIHA therapies.
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DOI：
10.1073/pnas.80.1.273
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
MATHIS, DJ;BENOIST, C;MCDEVITT, HO
通讯作者：
MCDEVITT, HO
DOI：
10.1084/jem.20062648
发表时间：
2007-07-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Caton ML;Smith-Raska MR;Reizis B
通讯作者：
Reizis B
影响因子：
3
作者：
Clausen, BE;Burkhardt, C;Förster, I
通讯作者：
Förster, I
影响因子：
14.9
作者：
Rickert, RC;Roes, J;Rajewsky, K
通讯作者：
Rajewsky, K
DOI：
10.3324/haematol.2012.065144
发表时间：
2012-12-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Hudson, Krystalyn E.;Hendrickson, Jeanne E.;Zimring, James C.
通讯作者：
Zimring, James C.