{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:35:17Z","timestamp":1791588917987,"version":"4.3.4"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T00:00:00Z","timestamp":1700092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intermittent itchy rash. Type 2 inflammatory cytokines such as interleukin (IL)-4, IL-13, and IL-31 are strongly implicated in AD pathogenesis. Stimulation of IL-31 cognate receptors on C-fiber nerve endings is believed to activate neurons in the dorsal root ganglion (DRG), causing itch. The IL-31 receptor is a heterodimer of OSMR\u03b2 and IL31RA subunits, and OSMR\u03b2 can also bind oncostatin M (OSM), a pro-inflammatory cytokine released by monocytes\/macrophages, dendritic cells, and T lymphocytes. Further, OSM expression is enhanced in the skin lesions of AD and psoriasis vulgaris patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The current study aimed to examine the contributions of OSM to AD pathogenesis and symptom expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The expression levels of the OSM gene (<jats:italic>OSM<\/jats:italic>) and various cytokine receptor genes were measured in human patient skin samples, isolated human monocytes, mouse skin samples, and mouse DRG by RT-qPCR. Itching responses to various pruritogens were measured in mice by counting scratching episodes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We confirmed overexpression of <jats:italic>OSM<\/jats:italic> in skin lesions of patients with AD and psoriasis vulgaris. Monocytes isolated from the blood of healthy subjects overexpressed <jats:italic>OSM<\/jats:italic> upon stimulation with IL-4 or GM-CSF. Systemic administration of OSM suppressed <jats:italic>IL31RA<\/jats:italic> expression in the mouse DRG and IL-31-stimulated scratching behavior. In contrast, systemic administration of OSM increased the expression of IL-4- and IL-13-related receptors in the DRG.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results suggest that OSM is an important cytokine in the regulation of skin monocytes, promoting the actions of IL-4 and IL-13 in the DRG and suppressing the action of IL-31. It is speculated that OSM released from monocytes in skin modulates the sensitivity of DRG neurons to type 2 inflammatory cytokines and thereby the severity of AD-associated skin itch.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1251031","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T13:35:52Z","timestamp":1700141752000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Oncostatin M suppresses IL31RA expression in dorsal root ganglia and interleukin-31-induced itching"],"prefix":"10.3389","volume":"14","author":[{"given":"Masataka","family":"Suehiro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomofumi","family":"Numata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozomi","family":"Yanagida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chie","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazue","family":"Uchida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhki","family":"Yanase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yozo","family":"Ishiuji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"McGrath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2020.02.006","article-title":"Japanese guidelines for atopic dermatitis 2020","volume":"69","author":"Katoh","year":"2020","journal-title":"Allergol Int"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31286-1","article-title":"Atopic dermatitis","volume":"396","author":"Langan","year":"2020","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20130351","article-title":"A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis","volume":"210","author":"Salimi","year":"2013","journal-title":"J Exp Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms21155382","article-title":"Regulation of filaggrin, loricrin, and involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: pathogenic implications in atopic dermatitis","volume":"21","author":"Furue","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B5","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1073\/pnas.93.6.2588","article-title":"Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch","volume":"171","author":"Oetjen","year":"2017","journal-title":"Cell"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01383","article-title":"Role of the pruritic cytokine IL-31 in autoimmune skin diseases","volume":"10","author":"Gibbs","year":"2019","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.ajhg.2007.09.002","article-title":"Oncostatin M receptor-\u03b2 mutations underlie familial primary localized cutaneous amyloidosis","volume":"82","author":"Arita","year":"2008","journal-title":"Am J Hum Genet"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2009.09311.x","article-title":"New insight into mechanisms of pruritus from molecular studies on familial primary localized cutaneous amyloidosis","volume":"161","author":"Tanaka","year":"2009","journal-title":"Br J Dermatol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3780220","article-title":"Oncostatin M production by blood and alveolar neutrophils during acute lung injury","volume":"81","author":"Grenier","year":"2001","journal-title":"Lab Invest"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.2002.1023","article-title":"Oncostatin M production by human dendritic cells in response to bacterial products","volume":"17","author":"Suda","year":"2002","journal-title":"Cytokine"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2015.07.006","article-title":"and interleukin-31: cytokines, receptors, signal transduction and physiology","volume":"26","author":"Hermanns HM. Oncostatin","year":"2015","journal-title":"Cytokine Growth Factor Rev"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abe3037","article-title":"Oncostatin M can sensitize sensory neurons in inflammatory pruritus","volume":"13","author":"Tseng","year":"2021","journal-title":"Sci Transl Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.7.4615","article-title":"Oncostatin M secreted by skin infiltrating T lymphocytes is a potent keratinocyte activator involved in skin inflammation","volume":"178","author":"Boniface","year":"2007","journal-title":"J Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119496","article-title":"Granulocyte macrophage colony-stimulating factor is overproduced by keratinocytes in atopic dermatitis. Implications for sustained dendritic cell activation in the skin","volume":"99","author":"Pastore","year":"1997","journal-title":"J Clin Invest"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI21060","article-title":"New insights into atopic dermatitis","volume":"113","author":"Leung","year":"2004","journal-title":"J Clin Invest"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.08.006","article-title":"CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells","volume":"93","author":"Zhou","year":"1996","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1005592","article-title":"IFN-\u03b1 promotes definitive maturation of dendritic cells generated by short-term culture of monocytes with GM-CSF and IL-4","volume":"80","author":"Dauer","year":"2006","journal-title":"J Leukoc Biol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1058963","article-title":"GM-CSF, Flt3-L and IL-4 affect viability and function of conventional dendritic cell types 1 and 2","volume":"13","author":"Lellahi","year":"2022","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201546216","article-title":"Oncostatin M overexpression induces skin inflammation but is not required in the mouse model of imiquimod-induced psoriasis-like inflammation","volume":"46","author":"Pohin","year":"2016","journal-title":"Eur J Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.10.048","article-title":"A sensory neuron-expressed IL-31 receptor mediates T helper cell-dependent itch: involvement of TRPV1 and TRPA1","volume":"133","author":"Cevikbas","year":"2014","journal-title":"J Allergy Clin Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.03.023","article-title":"Peripheral and central mechanisms of itch","volume":"98","author":"Dong","year":"2018","journal-title":"Neuron"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2022.04.003","article-title":"Peripheral itch sensitization in atopic dermatitis","volume":"71","author":"Tominaga","year":"2022","journal-title":"Allergol Int"},{"key":"B23","doi-asserted-by":"publisher","first-page":"4053","DOI":"10.3390\/ijms20164053","article-title":"IL-4 Augments IL-31\/IL-31 Receptor alpha interaction leading to enhanced Ccl 17 and Ccl 22 production in dendritic cells: implications for atopic dermatitis","volume":"20","author":"Miake","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2021.1940962","article-title":"The IL-4, IL-13 and IL-31 pathways in atopic dermatitis","volume":"17","author":"Dubin","year":"2021","journal-title":"Expert Rev Clin Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3881","article-title":"Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing","volume":"18","author":"Usoskin","year":"2015","journal-title":"Nat Neurosci"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1251031\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T13:36:15Z","timestamp":1700141775000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1251031\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,16]]},"references-count":25,"alternative-id":["10.3389\/fimmu.2023.1251031"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1251031","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,16]]},"article-number":"1251031"}}