{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:57:10Z","timestamp":1792270630660,"version":"4.4.0"},"reference-count":63,"publisher":"American Society for Clinical Investigation","issue":"1","license":[{"start":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T00:00:00Z","timestamp":1735776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AI078908,R37AI052353,R01AI136041,R01AI130109,R01AI175149,U19 AI095219,K22 AI146281"],"award-info":[{"award-number":["AI078908,R37AI052353,R01AI136041,R01AI130109,R01AI175149,U19 AI095219,K22 AI146281"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005292","name":"Brigham and Women\u2019s Hospital","doi-asserted-by":"crossref","award":["Hearst Young Investigator Award"],"award-info":[{"award-number":["Hearst Young Investigator Award"]}],"id":[{"id":"10.13039\/100005292","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,2]]},"abstract":"<jats:p>\n                    Mast cells (MCs) expressing a distinctive protease phenotype (MC\n                    <jats:sub>T<\/jats:sub>\n                    s) selectively expand within the epithelium of human mucosal tissues during type 2 (T2) inflammation. While MC\n                    <jats:sub>T<\/jats:sub>\n                    s are phenotypically distinct from subepithelial MCs (MC\n                    <jats:sub>TC<\/jats:sub>\n                    s), signals driving human MC\n                    <jats:sub>T<\/jats:sub>\n                    differentiation and this subset\u2019s contribution to inflammation remain unexplored. Here, we have identified TGF-\u03b2 as a key driver of the MC\n                    <jats:sub>T<\/jats:sub>\n                    transcriptome in nasal polyps. We found that short-term TGF-\u03b2 signaling alters MC cell surface receptor expression and partially recapitulated the in vivo MC\n                    <jats:sub>T<\/jats:sub>\n                    transcriptome, while TGF-\u03b2 signaling during MC differentiation upregulated a larger number of MC\n                    <jats:sub>T<\/jats:sub>\n                    -associated transcripts. TGF-\u03b2 inhibited the hallmark MC\n                    <jats:sub>TC<\/jats:sub>\n                    proteases chymase and cathepsin G at both the transcript and protein level, allowing selective in vitro differentiation of MC\n                    <jats:sub>T<\/jats:sub>\n                    s for functional study. We identified discrete differences in effector phenotype between in vitro\u2013derived MC\n                    <jats:sub>T<\/jats:sub>\n                    s and MC\n                    <jats:sub>TC<\/jats:sub>\n                    s, with MC\n                    <jats:sub>T<\/jats:sub>\n                    s exhibiting enhanced proinflammatory lipid mediator generation and a distinct cytokine, chemokine, and growth factor production profile in response to both innate and adaptive stimuli, recapitulating functional features of their tissue-associated counterpart MC subsets. Thus, our findings support a role for TGF-\u03b2 in promoting human MC\n                    <jats:sub>T<\/jats:sub>\n                    differentiation and identified a discrete contribution of this cell type to T2 inflammation.\n                  <\/jats:p>","DOI":"10.1172\/jci174981","type":"journal-article","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T14:00:42Z","timestamp":1735740042000},"source":"Crossref","is-referenced-by-count":13,"title":["Human intraepithelial mast cell differentiation and effector function are directed by TGF-\u03b2 signaling"],"prefix":"10.1172","volume":"135","author":[{"given":"Tahereh","family":"Derakhshan","sequence":"first","affiliation":[{"name":"Jeff and Penny Vinik Center for Allergic Disease Research, Division of Allergy and Clinical Immunology, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."},{"name":"Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Hollers","sequence":"additional","affiliation":[{"name":"Jeff and Penny Vinik Center for Allergic Disease Research, Division of Allergy and Clinical Immunology, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Perniss","sequence":"additional","affiliation":[{"name":"Jeff and Penny Vinik Center for Allergic Disease Research, Division of Allergy and Clinical Immunology, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."},{"name":"Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa","family":"Ryan","sequence":"additional","affiliation":[{"name":"Jeff and Penny Vinik Center for Allergic Disease Research, Division of Allergy and Clinical Immunology, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alanna","family":"McGill","sequence":"additional","affiliation":[{"name":"Jeff and Penny Vinik Center for Allergic Disease Research, Division of Allergy and Clinical Immunology, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Hacker","sequence":"additional","affiliation":[{"name":"Jeff and Penny Vinik Center for Allergic Disease Research, Division of Allergy and Clinical Immunology, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regan W.","family":"Bergmark","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Department of Surgery, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Bhattacharyya","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Department of Otolaryngology, Massachusetts Eye and Ear, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella E.","family":"Lee","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Department of Surgery, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice Z.","family":"Maxfield","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Department of Surgery, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7899-6336","authenticated-orcid":true,"given":"Rachel E.","family":"Roditi","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Department of Surgery, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1141-1529","authenticated-orcid":true,"given":"Lora","family":"Bankova","sequence":"additional","affiliation":[{"name":"Jeff and Penny Vinik Center for Allergic Disease Research, Division of Allergy and Clinical Immunology, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."},{"name":"Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M.","family":"Buchheit","sequence":"additional","affiliation":[{"name":"Jeff and Penny Vinik Center for Allergic Disease Research, Division of Allergy and Clinical Immunology, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."},{"name":"Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya M.","family":"Laidlaw","sequence":"additional","affiliation":[{"name":"Jeff and Penny Vinik Center for Allergic Disease Research, Division of Allergy and Clinical Immunology, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."},{"name":"Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua A.","family":"Boyce","sequence":"additional","affiliation":[{"name":"Jeff and Penny Vinik Center for Allergic Disease Research, Division of Allergy and Clinical Immunology, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."},{"name":"Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel F.","family":"Dwyer","sequence":"additional","affiliation":[{"name":"Jeff and Penny Vinik Center for Allergic Disease Research, Division of Allergy and Clinical Immunology, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."},{"name":"Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,1,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.07.003"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1997.77.4.1033"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abb7221"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.02.046"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.04.009"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201002-0295OC"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/0091-6749(92)90444-7"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.03.003"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2012.02836.x"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1172\/JCI126402"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200321"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0449-8"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.67.3.350"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-10-183"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58815"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032713-120257"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abq6352"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.06.029"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1369\/0022155412458927"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/23488"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.7.3461"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2009.23.3412"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.02.00205402"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.11.6751"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.01.056"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85538"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2003.11.007"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.10.5987"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601983"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3390\/cells10051033"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.09.021"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.09.059"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.1.187"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503948102"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2016-0307TR"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2010-0027TR"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.10.012"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.16.5788"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2008.01.012"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.14.10.1362"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2002.282.1.L115"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.108.6.2241"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2006.063487"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2004.01885.x"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.156.2.9605065"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.07.010"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.158.6.9803053"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.10.002"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2006.10.016"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14144-8"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-017-0014-7"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201412-2278OC"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.155.1.297"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.02.035"},{"issue":"4","key":"B56","first-page":"173","article-title":"Clinical factors influencing the eosinophil infiltration of nasal polyps","volume":"40","author":"Jankowski","year":"2002","journal-title":"Rhinology"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01865-2021"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.07.056"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31881-1"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/0091-6749(94)90123-6"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2003.1387"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.12.958"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2266"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/174981\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T22:47:27Z","timestamp":1779230847000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/174981"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,2]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1,2]]},"published-print":{"date-parts":[[2025,1,2]]}},"alternative-id":["10.1172\/JCI174981"],"URL":"https:\/\/doi.org\/10.1172\/jci174981","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,2]]},"article-number":"e174981"}}