The Journal of allergy and clinical immunology · 2019
Noncanonical autophagy in dermal dendritic cells mediates immunosuppressive effects of UV exposure.
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СтатьяПоддержка NIH: внешняя программаResearch Support, N.I.H., IntramuralПоддержка исследования: вне правительства СШАОтозванная публикацияНазвание и аннотация: Перевод пока не подготовлен
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Sil Payel, Suwanpradid Jutamas, Muse Ginger, Gruzdev Artiom, Liu Liwen, Corcoran David L, Willson Cynthia J, Janardhan Kyathanahalli, Grimm Sara, Myers Page, Degraff Laura Miller, MacLeod Amanda S, Martinez Jennifer
Аннотация
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.
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.