Non-canonical autophagy in dermal dendritic cells mediates immunosuppressive effects of UV exposure

Non-canonical autophagy in dermal dendritic cells mediates immunosuppressive effects of UV exposure:

Publication date: Available online 16 December 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Payel Sil, Jutamas Suwanpradid, Ginger Muse, Artiom Gruzdev, Liwen Liu, David L. Corcoran, Cynthia J. Willson, Kyathanahalli Janardhan, Sara Grimm, Page Myers, Laura Miller Degraff, Amanda S. MacLeod, Jennifer Martinez

Abstract

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. While defects in autophagy machinery have been associated with inflammatory pathologies, we now appreciate that autophagic components participate in non-canonical pathways distinct from classical autophagy. We have previously demonstrated that LC3-associated phagocytosis (LAP), a non-canonical autophagic process dependent on Rubicon (RUBCN), contributes to immunosuppression.

Objective

We used Rubcn^-/- mice to examine the role of in mediating the UV-induced immunotolerant program in a model of contact hypersensitivity (CHS).

Methods

Flow cytometry and transcriptional analysis was 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 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 contact hypersensitivity (CHS). Specifically, RUBCN deficiency in CD301b⁺ dermal dendritic cells (dDC2s) 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.

Graphical abstract