{"id":{"repo_id":"washington","oai_identifier":"oai:digital.lib.washington.edu:1773/51188"},"canonical_url":"https://search.dev.ndltd.org/etd/washington/oai:digital.lib.washington.edu:1773/51188","repository":{"repo_id":"washington","name":"University of Washington","base_url":"https://digital.lib.washington.edu/server/oai/request"},"display":{"title":"Prolonged T – DC macro-clustering within lymph node microenvironments initiates Th2 differentiation in a site-specific manner","abstract":"T helper 2 (Th2) responses protect against pathogens while also driving allergic inflammation, yet how large-scale Th2 responses are generated in tissue context remains unclear. Here, we used quantitative imaging to investigate early Th2 differentiation within lymph nodes (LNs) following cutaneous allergen administration. Contrary to current models, we observed extensive activation and ‘macro-clustering’ of early Th2 cells with migratory type-2 dendritic cells (cDC2s) generating specialized Th2-promoting microenvironments. Macro-clustering was integrin mediated and promoted localized cytokine exchange among T cells to reinforce differentiation, which contrasted behavior during Th1 responses. Unexpectedly, formation of Th2 macro-clusters was dependent on the site of skin sensitization. Differences between sites were driven by divergent activation states of migratory cDC2 across dermal tissues, with enhanced costimulatory molecule expression by cDC2 in Th2-generating LNs promoting prolonged T cell activation, macro-clustering, and cytokine sensing. Thus, generation of dedicated Th2 priming micro-environments through enhanced costimulatory molecule signaling initiates Th2 responses in vivo and occurs in a skin site-specific manner.","abstract_html":"T helper 2 (Th2) responses protect against pathogens while also driving allergic inflammation, yet how large-scale Th2 responses are generated in tissue context remains unclear. Here, we used quantitative imaging to investigate early Th2 differentiation within lymph nodes (LNs) following cutaneous allergen administration. Contrary to current models, we observed extensive activation and ‘macro-clustering’ of early Th2 cells with migratory type-2 dendritic cells (cDC2s) generating specialized Th2-promoting microenvironments. Macro-clustering was integrin mediated and promoted localized cytokine exchange among T cells to reinforce differentiation, which contrasted behavior during Th1 responses. Unexpectedly, formation of Th2 macro-clusters was dependent on the site of skin sensitization. Differences between sites were driven by divergent activation states of migratory cDC2 across dermal tissues, with enhanced costimulatory molecule expression by cDC2 in Th2-generating LNs promoting prolonged T cell activation, macro-clustering, and cytokine sensing. Thus, generation of dedicated Th2 priming micro-environments through enhanced costimulatory molecule signaling initiates Th2 responses in vivo and occurs in a skin site-specific manner.","abstract_has_math":false,"creators":["Lyons-Cohen, Miranda R."],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Gerner, Michael Y"],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-02-12","date_published":"2024-02-12","updated_at":"2026-07-24T05:58:14Z","subjects":["Immunology","Cellular biology","Biology"],"languages":["en_US"],"rights":["CC BY"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1773/51188","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Gerner, Michael Y"]},{"key":"dc:creator","label":"Author","values":["Lyons-Cohen, Miranda R."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-02-12T23:41:05Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2024-02-12T23:41:05Z"]},{"key":"dc:date.issued","label":"Date","values":["2024-02-12"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Immunology","Cellular biology","Biology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_US"]},{"key":"dc:rights","label":"Dc Rights","values":["CC BY"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["LyonsCohen_washington_0250E_26467.pdf"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1773/51188"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Thesis (Ph.D.)--University of Washington, 2023"]},{"key":"dc:description.abstract","label":"Abstract","values":["T helper 2 (Th2) responses protect against pathogens while also driving allergic inflammation, yet how large-scale Th2 responses are generated in tissue context remains unclear. Here, we used quantitative imaging to investigate early Th2 differentiation within lymph nodes (LNs) following cutaneous allergen administration. Contrary to current models, we observed extensive activation and ‘macro-clustering’ of early Th2 cells with migratory type-2 dendritic cells (cDC2s) generating specialized Th2-promoting microenvironments. Macro-clustering was integrin mediated and promoted localized cytokine exchange among T cells to reinforce differentiation, which contrasted behavior during Th1 responses. Unexpectedly, formation of Th2 macro-clusters was dependent on the site of skin sensitization. Differences between sites were driven by divergent activation states of migratory cDC2 across dermal tissues, with enhanced costimulatory molecule expression by cDC2 in Th2-generating LNs promoting prolonged T cell activation, macro-clustering, and cytokine sensing. Thus, generation of dedicated Th2 priming micro-environments through enhanced costimulatory molecule signaling initiates Th2 responses in vivo and occurs in a skin site-specific manner."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Prolonged T – DC macro-clustering within lymph node microenvironments initiates Th2 differentiation in a site-specific manner"]}]}],"canonical_facts":{"dc:contributor.advisor":["Gerner, Michael Y"],"dc:creator":["Lyons-Cohen, Miranda R."],"dc:date.accessioned":["2024-02-12T23:41:05Z"],"dc:date.available":["2024-02-12T23:41:05Z"],"dc:date.issued":["2024-02-12"],"dc:description":["Thesis (Ph.D.)--University of Washington, 2023"],"dc:description.abstract":["T helper 2 (Th2) responses protect against pathogens while also driving allergic inflammation, yet how large-scale Th2 responses are generated in tissue context remains unclear. 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Thus, generation of dedicated Th2 priming micro-environments through enhanced costimulatory molecule signaling initiates Th2 responses in vivo and occurs in a skin site-specific manner."],"dc:format.mimetype":["application/pdf"],"dc:identifier.other":["LyonsCohen_washington_0250E_26467.pdf"],"dc:identifier.uri":["http://hdl.handle.net/1773/51188"],"dc:language.iso":["en_US"],"dc:rights":["CC BY"],"dc:subject":["Immunology","Cellular biology","Biology"],"dc:title":["Prolonged T – DC macro-clustering within lymph node microenvironments initiates Th2 differentiation in a site-specific manner"],"dc:type":["Thesis"]},"updated_at":"2026-07-24T05:58:14Z"}