Lymphatic Regulation and Photosensitivity
For some patients with lupus, exposure to the sun—or even certain kinds of indoor lighting — can trigger skin inflammation, joint pain, fever, and other symptoms. The lymphatic system, a network of tubes that transports fluid and cells throughout the body, normally limits inflammation and swelling. However, patients with lupus have high levels of type I interferons; we believe this excess of type I interferons reduces lymphatic circulation throughout the body, thereby promoting photosensitivity.
To test this hypothesis, Dr. Lu and her team will measure fluid movement through lymphatic vessels in mice and patients with lupus. They will also test in mice whether stimulating circulation in the lymphatic system can reduce photosensitivity. These studies will show if lymphatic vessels are a good target for future drugs to treat photosensitivity.
What this study means for people with lupus
Many people with lupus are extremely sensitive to light and can develop a rash or other painful symptoms after just minutes in the sun. Dr. Lu’s team aims to discover if this photosensitivity is caused by reduced flow in the lymphatic system, a network of tubes that transports fluid and cells throughout the body. Their results could open a new avenue for treating lupus photosensitivity, possibly even with certain types of massage that stimulate lymphatic circulation.
Photosensitivity is a feature of systemic lupus erythematosus (SLE) as well as cutaneous lupus erythematosus (CLE) whereby the skin is sensitive to ultraviolet radiation (UVR), and even ambient sunlight exposure can lead to the development of inflammatory skin lesions. The lesions can be disfiguring and can be associated with flares of systemic disease characterized by increased autoantibody titers and worsening nephritis. However, the mechanisms that promote or limit photosensitivity are poorly understood. Lymphatic vessels are essential for moving fluid, solutes, and cells out of tissue to limit and resolve tissue inflammation. Lack of adequate lymphatic flow can increase and prolong tissue inflammation. Type I interferon has been linked to lymphatic leakiness and reduced flow. Lymphatic function has not been well-studied in SLE, but it is plausible that the increased type I interferon in SLE induces lymphatic dysfunction that contributes to photosensitivity. Here we characterize photosensitivity in both the MLR/lpr and B6.Sle1.yaa models of SLE. We also show that poly I:C increases vascular permeability and reduces lymphatic flow. Based on the literature and these preliminary data, we hypothesize that high levels of type I interferon in SLE induces lymphatic dysfunction in SLE, thus contributing to photosensitivity, and that improving lymphatic flow may ameliorate photosensitivity. This understanding has implications for potentially ameliorating photosensitivity by using therapies such as pharmacologic agents or manual techniques such as lymphatic massage to improve lymphatic flow. Understanding about the flow of information from the skin to draining lymph nodes may also lay the groundwork for better understanding how systemic flares can also be triggered by UVR in SLE. We propose to test the following Specific Aims:
1. Characterize lymphatic function in SLE models and patients and understand the role of type I interferon in lymphatic function and photosensitivity.
2. Understand the extent to which manipulating lymphatics modulates photosensitivity in SLE models.