被撤回的出版物: Noncanonical autophagy in dermal dendritic cells mediates immunosuppressive effects of UV exposure (Retracted article. See vol. 150, pg. 979, 2022)

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:145

Article; Retracted Publication

Sil, Payel¹  Suwanpradid, Jutamas⁵  Muse, Ginger¹  Gruzdev, Artiom²  Liu, Liwen³  Corcoran, David L.⁸  Willson, Cynthia J.⁹  Janardhan, Kyathanahalli⁹  Grimm, Sara¹⁰  Myers, Page⁴  Degraff, Laura Miller¹  MacLeod, Amanda S.^5,6,7  Martinez, Jennifer¹ 

[1] NIEHS, Immun Inflammat & Dis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA

[2] NIEHS, Knockout Mouse Core Lab, Reprod & Dev Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA

[3] NIEHS, Mol Genom Core Lab, Signal Transduct Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA

[4] NIEHS, Comparat Med Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA

[5] Duke Univ, Dept Dermatol, Durham, NC USA

[6] Duke Univ, Dept Immunol, Durham, NC USA

[7] Duke Univ, Dept Mol Genet & Microbiol, Durham, NC USA

[8] Duke Univ, Med Ctr, Duke Ctr Genom & Computat Biol, Durham, NC USA

[9] Integrated Lab Syst Inc, Res Triangle Pk, NC USA

[10] Div Intramural Res, Res Triangle Pk, NC USA

关键词: Autophagy;    LAP;    Rubicon;    contact hypersensitivity;    inflammation;    efferocytosis;    antigen presentation;    dendritic cells;   

DOI  :  10.1016/j.jaci.2019.11.041

来源: Elsevier

【 摘 要 】

Background: Control of the inflammatory response is critical to maintaining homeostasis, and failure to do so contributes to the burden of chronic inflammation associated with several disease states. The mechanisms that underlie immunosuppression, however, remain largely unknown. Although defects in autophagy machinery have been associated with inflammatory pathologic conditions, we now appreciate that autophagic components participate in noncanonical pathways distinct from classical autophagy. We have previously demonstrated that LC3-associated phagocytosis (LAP), a noncanonical autophagic process dependent on Rubicon (rubicon autophagy regulator [RUBCN]), contributes to immunosuppression. Objective: We used Rubcn(-/-) mice to examine the role of the LAP pathway in mediating the UV-induced immunotolerant program in a model of contact hypersensitivity (CHS). Methods: Flow cytometry and transcriptional analysis were used to measure immune cell infiltration and activation in the skin of Rubcn(+/+) and Rubcn(-/-) mice during the CHS response. Results: Here, we demonstrate that LAP is required for UV-induced immunosuppression and that UV exposure induces a broadly anti-inflammatory transcriptional program dependent on Rubicon. Rubcn(-/-) mice are resistant to UV-induced immunosuppression and instead display exaggerated inflammation in a model of CHS. Specifically, RUBCN deficiency in CD301b(+) dermal dendritic cells results in their increased antigen presentation capacity and subsequent hyperactivation of the CD8(+) T-cell response. Conclusions: LAP functions to limit the immune response and is critical in maintaining the balance between homeostasis and inflammation.

【 授权许可】

Free