Inflammatory reactions to the sun, also known as photosensitivity, have been observed in numerous autoimmune diseases and can result in disease flares.
It’s believed that photosensitivity is caused by elevated levels of proteins in the skin called type 1 interferons, or IFN, that make the skin prone to enhanced inflammation.
Despite this knowledge, the factors that lead to inflammatory response from UV light aren’t well known.
A research team at University of Michigan Health, led by Benjamin Klein, M.D., a postdoctoral fellow in the lab of Michelle Kahlenberg at the University of Michigan, decided to take a deeper look at the impact of IFN and UV irradiation in skin cells.
The results of the study, published in Science Immunology, identified that in adult and pediatric lupus and dermatomyositis skin, the protein ZBP1 is chronically upregulated.
After UV light hits the skin, ZBP1 binds critical factors, called Z-DNA, that get released.
Together this complex causes strong activation of the immune system in the skin, explaining why inflammation is so prevalent after UV light exposure in autoimmune photosensitive patients.
These results have important implications when it comes to the treatment and prevention of cutaneous and systemic flares of photosensitivity in autoimmune diseases.
“The skin is the most commonly affected organ in lupus patients, so making sure that we can protect it from taking on significant damage from UV light is crucial,” said Klein.
“Identifying both Z-DNA and ZBP1 as regulators and potential treatment targets in photosensitivity is another steppingstone in learning more about how we can better protect the skin from harmful lesions caused by UV irradiation.”
Further research will be needed to begin learning how best to treat photosensitivity using this new information.
Currently, the best treatment for photosensitivity is diligent sunscreen usage.
Paper cited: “Epidermal ZBP1 stabilizes mitochondrial Z-DNA to drive UV-induced IFN signaling in autoimmune photosensitivity,” Science Immunology. DOI: 10.1126/sciimmunol.ado1710
Additional authors: Bin Xu, Yiqing Gao, Svenja Henning, Shannon N. Loftus, Kelsey E. McNeely and Amanda M. Victory from the Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor. Mack B. Reynolds and Mary X. O’Riordan from the Department of Microbiology and Immunology, University of Michigan, Ann Arbor. Craig Dobry, Grace A. Hile and Johann E. Gudjonsson from the Department of Dermatology, University of Michigan, Ann Arbor. Celine C. Berthier from the Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor. Christine M. Goudsmit and Jessica L. Turnier from the Division of Pediatric Rheumatology, Department of Pediatrics, University of Michigan, Ann Arbor. Mehrnaz Gharaee-Kermani, Feiyang Ma and J. Michelle Kahlenberg from the Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor and the Department of Dermatology, University of Michigan, Ann Arbor. Lam C. Tsoi from the Department of Dermatology, University of Michigan, Ann Arbor, Department of Biostatistics, University of Michigan, Ann Arbor and the Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor.
Funding/disclosures: This work was supported by the National Institutes of Health through awards R01AR071384, K24AR076975, R03AR066337 (JMK), P30AR075043 (JEG), R01AI157384, (MOR), K23AR080789 (JLT), German Research Foundation fund KL3612/1-1 (BK), Rheumatology Research Foundation Investigator Award 025850 (JLT), Cure JM Award Michigan12/20 (JLT), University of Michigan Immunology Program Research Training in Experimental Immunology training grant T32 AI007413 (MR), Miller Fund Award for Innovative Immunology Research (MR), American Heart Association and Barth Syndrome Foundation co-funded predoctoral fellowship 23PRE1019408 (MR), the George M. O’Brien Michigan Kidney Translational Resource Center (MKTC) NIH/MIDDK grant U54DK137314 (CB) and the Taubman Institute Innovative Programs (JMK and JEG).
Tech transfer(s)/Conflict(s) of interest: JMK has received grant support from Q32 Bio, Celgene/Bristol-Myers Squibb, Ventus Therapeutics, Rome Therapeutics, and Janssen. JMK has served on advisory boards for AstraZeneca, Biogen, Bristol-Myers Squibb, Eli Lilly, EMD serrano, Exo Therapeutics, Gilead, GlaxoSmithKline, Aurinia Pharmaceuticals, Rome Therapeutics, Synthekine, Vivideon, and Ventus Therapeutics. JEG has received support from Eli Lilly, Janssen, BMS, Sanofi, Prometheus, Almirall, Kyowa-Kirin, Novartis, AnaptysBio, Boehringer Ingelheim, Regeneron, AbbVie, and Galderma.
Michigan Research Core(s): Advanced Genomics Core, Microscopy Core, Rogel Cancer Center Immunology core.
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Previously Published on michiganmedicine.org with Creative Commons License
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