{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T23:19:19Z","timestamp":1770679159269,"version":"3.49.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"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":[[2017,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Copper has previously been implicated in the regulation of immune responses, but the impact of this metal on mast cells is poorly understood. In this article, we address this issue and show that copper starvation of mast cells causes increased granule maturation, as indicated by higher proteoglycan content, stronger metachromatic staining, and altered ultrastructure in comparison with nontreated cells, whereas copper overload has the opposite effects. In contrast, copper status did not impact storage of histamine in mast cells, nor did alterations in copper levels affect the ability of mast cells to degranulate in response to IgER cross-linking. A striking finding was decreased tryptase content in mast cells with copper overload, whereas copper starvation increased tryptase content. These effects were associated with corresponding shifts in tryptase mRNA levels, suggesting that copper affects tryptase gene regulation. Mechanistically, we found that alterations in copper status affected the expression of microphthalmia-associated transcription factor, a transcription factor critical for driving tryptase expression. We also found evidence supporting the concept that the effects on microphthalmia-associated transcription factor are dependent on copper-mediated modulation of MAPK signaling. Finally, we show that, in MEDNIK syndrome, a condition associated with low copper levels and a hyperallergenic skin phenotype, including pruritis and dermatitis, the number of tryptase-positive mast cells is increased. Taken together, our findings reveal a hitherto unrecognized role for copper in the regulation of mast cell gene expression and maturation.<\/jats:p>","DOI":"10.4049\/jimmunol.1700786","type":"journal-article","created":{"date-parts":[[2017,11,10]],"date-time":"2017-11-10T17:10:14Z","timestamp":1510333814000},"page":"4132-4141","source":"Crossref","is-referenced-by-count":16,"title":["Copper Regulates Maturation and Expression of an MITF:Tryptase Axis in Mast Cells"],"prefix":"10.1093","volume":"199","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1326-6698","authenticated-orcid":false,"given":"Jun Mei","family":"Hu Frisk","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Uppsala University , 75123 Uppsala,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lena","family":"Kjell\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Uppsala University , 75123 Uppsala,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7522-926X","authenticated-orcid":false,"given":"Stephen G","family":"Kaler","sequence":"additional","affiliation":[{"name":"Section on Translational Neuroscience, Molecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunnar","family":"Pejler","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Uppsala University , 75123 Uppsala,","place":["Sweden"]},{"name":"Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences , 75007 Uppsala,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena","family":"\u00d6hrvik","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Uppsala University , 75123 Uppsala,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,12,15]]},"reference":[{"key":"2025030614543639500_r1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.immuni.2012.07.003","article-title":"Developmental origin and functional specialization of mast cell subsets","volume":"37","author":"Gurish","year":"2012","journal-title":"Immunity"},{"key":"2025030614543639500_r2","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/nri2327","article-title":"Immunomodulatory mast cells: negative, as well as positive, regulators of immunity","volume":"8","author":"Galli","year":"2008","journal-title":"Nat. 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