{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:37:26Z","timestamp":1791459446117,"version":"4.3.4"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T00:00:00Z","timestamp":1427846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>UV radiation (UVR) induces DNA damage, leading to the accumulation of mutations in epidermal keratinocytes and immunosuppression, which contribute to the development of nonmelanoma skin cancer. We reported previously that the TLR4\u2013MyD88 signaling axis is necessary for UV-induced apoptosis. In the dinitrofluorobenzene contact hypersensitivity model, UV-irradiated MyD88-deficient (MyD88\u2212\/\u2212) C57BL\/6 mice had intact ear swelling, exaggerated inflammation, and higher levels of dinitrofluorobenzene-specific IgG2a compared with wild-type (WT) mice. Even with normal UV-induced, dendritic cell migration, DNA damage in the local lymph nodes was less pronounced in MyD88\u2212\/\u2212 mice compared with WT mice. Cultured, UV-irradiated WT APCs showed cleavage (inactivation) of the DNA damage\u2013recognition molecule PARP, whereas PARP persisted in MyD88\u2212\/\u2212 and TLR4\u2212\/\u2212 APCs. Epidermal DNA from in vivo UV-irradiated MyD88\u2212\/\u2212 mice had an increased resolution rate of cyclobutane pyrimidine dimers. Both in vitro treatment of MyD88\u2212\/\u2212 APCs with and intradermal in vivo injections of PARP inhibitor, PJ-34, caused WT-level cyclobutane pyrimidine dimer repair. Lymphoblasts deficient in DNA repair (derived from a xeroderma pigmentosum group A patient) failed to augment DNA repair after MyD88 knockdown after UVR, in contrast to lymphoblasts from a healthy control. These data suggest that interference with the TLR4\/MyD88 pathway may be a useful tool in promoting DNA repair and maintaining immune responses following UVR-induced damage.<\/jats:p>","DOI":"10.4049\/jimmunol.1402583","type":"journal-article","created":{"date-parts":[[2015,2,26]],"date-time":"2015-02-26T17:42:35Z","timestamp":1424972555000},"page":"3127-3135","source":"Crossref","is-referenced-by-count":22,"title":["Ultraviolet Radiation Signaling through TLR4\/MyD88 Constrains DNA Repair and Plays a Role in Cutaneous Immunosuppression"],"prefix":"10.1093","volume":"194","author":[{"given":"Erin","family":"Harberts","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland , Baltimore, MD 21201"},{"name":"Department of Dermatology, University of Maryland , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Maryland , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Fishelevich","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Maryland , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Maryland , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony A","family":"Gaspari","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland , Baltimore, MD 21201"},{"name":"Department of Dermatology, University of Maryland , Baltimore, MD 21201"},{"name":"Research Service, Baltimore Veterans Affairs Medical Center , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,4,1]]},"reference":[{"key":"2025030705402485000_r1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/1011-1344(95)07166-1","article-title":"Biological dosimetry and action spectra","volume":"31","author":"Tyrrell","year":"1995","journal-title":"J. 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