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Despite their profound effects on tissue physiology, Th2 cells represent a rare cell population within tissues, suggesting mechanisms restraining Th2 cell expansion at barrier sites that remain ill defined. Using a murine model of allergic asthma, we demonstrate that effector Th2 cells promote cDC2 activation within the lungs, including expression of the CCR4 ligands that attract Foxp3\n                  <jats:sup>+<\/jats:sup>\n                  regulatory T cells (Tregs). Selective deletion of\n                  <jats:italic>Ccr4<\/jats:italic>\n                  in Tregs during the effector Th2 cell response led to increased lung Th2 cells, activated cDC2s, and allergic inflammation.\n                <\/jats:p>\n                <jats:p>Mechanistically, CCR4 promoted Treg trafficking efficiency and was required to specifically control tissue cDC2 co-stimulatory molecule expression. Lastly, in the airways of humans with allergy, the expression of the CCR4 ligands in activated cDCs correlated with Treg enrichment. In sum, we define a cDC2-Treg feedback circuit within a barrier tissue that restrains effector Th2 cell expansion, revealing a novel role for tissue cDC2s in controlling Th2 cell biology.<\/jats:p>","DOI":"10.64898\/2026.05.04.722795","type":"posted-content","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T12:45:08Z","timestamp":1778244308000},"source":"Crossref","is-referenced-by-count":0,"title":["Type 2 conventional dendritic cells and regulatory T cells form a barrier tissue circuit to control allergic inflammation"],"prefix":"10.64898","author":[{"given":"Jenny M.","family":"Mannion","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Mass General Brigham, Boston, MA, USA"},{"name":"Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Mass General Brigham, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7998-5484","authenticated-orcid":false,"given":"Lukas M.","family":"Altenburger","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Mass General Brigham, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Willit","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Mass General Brigham, Boston, MA, USA"},{"name":"Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Mass General Brigham, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1394-3158","authenticated-orcid":false,"given":"Neal P.","family":"Smith","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Mass General Brigham, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Creel Ng","family":"Cashin","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Mass General Brigham, Boston, MA, USA"},{"name":"Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Mass General Brigham, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonah","family":"Clegg","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Mass General Brigham, Boston, MA, USA"},{"name":"Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Mass General Brigham, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nandini","family":"Samanta","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Mass General Brigham, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Barrera","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Harvard Chan Bioinformatics Core, Havard T.H. 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