Lymphatic dysfunction in lupus contributes to cutaneous photosensitivity and lymph node B cell responses

Abstract

ABSTRACTPhotosensitivity in lupus and subsequent systemic disease flares contribute to disease burden and is incompletely understood. Skin communicates with lymphoid tissues via lymphatics and reduced lymphatic flow in murine models results in skin inflammation and autoimmunity. Here, we demonstrate that the skin of lupus patients and multiple murine lupus models are characterized by lymphatic flow dysfunction. Improving lymphatic flow in murine lupus models via manual lymphatic drainage or by utilizing a transgenic model with increased lymphatics ameliorated cutaneous photosensitivity and diminished draining lymph node germinal center B cell and plasmablast responses. Improved lymphatic flow limited B cell responses via acting on a stromal-immune circuit previously described by our lab. Increased lymphatic flow increases stromal CCL2, which modulates monocyte function and limits B cell responses. This work provides a link between cutaneous photosensitivity and systemic disease in lupus and suggests that improving lymphatic flow or targeting the lymph node microenvironment could be potential therapeutic targets.