{"id":{"repo_id":"penn","oai_identifier":"oai:repository.upenn.edu:20.500.14332/62257"},"canonical_url":"https://search.dev.ndltd.org/etd/penn/oai:repository.upenn.edu:20.500.14332/62257","repository":{"repo_id":"penn","name":"University of Pennsylvania","base_url":"https://repository.upenn.edu/server/oai/request"},"display":{"title":"SKIN COMMENSAL STAPHYLOCOCCUS PROMOTES SYSTEMIC V-GAMMA-6 GAMMA-DELTA T CELL RECONFIGURATION","abstract":"The gut microbiota is known to regulate both local immune responses and systemic functions in healthy hosts. However, it remains unclear whether the skin microbiota – resident on the body's largest barrier – can influence systemic responses. Skin-resident Staphylococcus aureus is a common commensal bacterium found in healthy individuals. This study demonstrates that, in mice, skin colonization by topical association with S. aureus reshapes systemic lymphocyte pools across lymphoid and non-lymphoid tissues. Notably, S. aureus skin colonization promotes a robust expansion of IL-17A-producing Vγ6⁺ γδT cells both locally in the dermis and systemically in lymphoid, mucosal, metabolic and central nervous system tissues. This systemic reconfiguration is IL-1R-dependent but independent of IL-23 receptor signaling and the endogenous microbiota. Transcriptomic profiling reveals a transitional state in dermal Vγ6⁺ γδT cells from skin colonized mice, marked by changes in tissue-residency and migration-associated genes. Lymphatic trafficking, proliferation and long-term recirculation sustain this response. These findings provide the first evidence that a localized commensal skin microbe can robustly reshape systemic γδT17 cell populations, with potentially distal functional consequences, offering new insights into how skin commensals dynamically tune allostatic setpoints. This hitherto unrecognized allostatic process by which discrete skin microbial signals can systemically recalibrate tissue IL-17 landscape and may represent a novel modality for harnessing microbiome-mediated γδT17 cells in treating metabolic, infectious, and inflammatory diseases.","abstract_html":"The gut microbiota is known to regulate both local immune responses and systemic functions in healthy hosts. However, it remains unclear whether the skin microbiota – resident on the body's largest barrier – can influence systemic responses. Skin-resident Staphylococcus aureus is a common commensal bacterium found in healthy individuals. This study demonstrates that, in mice, skin colonization by topical association with S. aureus reshapes systemic lymphocyte pools across lymphoid and non-lymphoid tissues. Notably, S. aureus skin colonization promotes a robust expansion of IL-17A-producing Vγ6⁺ γδT cells both locally in the dermis and systemically in lymphoid, mucosal, metabolic and central nervous system tissues. This systemic reconfiguration is IL-1R-dependent but independent of IL-23 receptor signaling and the endogenous microbiota. Transcriptomic profiling reveals a transitional state in dermal Vγ6⁺ γδT cells from skin colonized mice, marked by changes in tissue-residency and migration-associated genes. Lymphatic trafficking, proliferation and long-term recirculation sustain this response. These findings provide the first evidence that a localized commensal skin microbe can robustly reshape systemic γδT17 cell populations, with potentially distal functional consequences, offering new insights into how skin commensals dynamically tune allostatic setpoints. This hitherto unrecognized allostatic process by which discrete skin microbial signals can systemically recalibrate tissue IL-17 landscape and may represent a novel modality for harnessing microbiome-mediated γδT17 cells in treating metabolic, infectious, and inflammatory diseases.","abstract_has_math":false,"creators":["Rao, Indira, N"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Belkaid, Yasmine","Dang, Eric, V"],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025","date_published":"2025","updated_at":"2026-07-24T03:45:38Z","subjects":["Immunology and Infectious Disease","Biology"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://repository.upenn.edu/handle/20.500.14332/62257","outbound_label":"Repository record","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Belkaid, Yasmine","Dang, Eric, V"]},{"key":"dc:creator","label":"Author","values":["Rao, Indira, N"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2026-01-29T17:16:16Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2026-01-29T17:16:16Z"]},{"key":"dc:date.issued","label":"Date","values":["2025"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation/Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Immunology and Infectious Disease","Biology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://repository.upenn.edu/handle/20.500.14332/62257"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["2025"]},{"key":"dc:description.abstract","label":"Abstract","values":["The gut microbiota is known to regulate both local immune responses and systemic functions in healthy hosts. However, it remains unclear whether the skin microbiota – resident on the body's largest barrier – can influence systemic responses. Skin-resident Staphylococcus aureus is a common commensal bacterium found in healthy individuals. This study demonstrates that, in mice, skin colonization by topical association with S. aureus reshapes systemic lymphocyte pools across lymphoid and non-lymphoid tissues. Notably, S. aureus skin colonization promotes a robust expansion of IL-17A-producing Vγ6⁺ γδT cells both locally in the dermis and systemically in lymphoid, mucosal, metabolic and central nervous system tissues. This systemic reconfiguration is IL-1R-dependent but independent of IL-23 receptor signaling and the endogenous microbiota. Transcriptomic profiling reveals a transitional state in dermal Vγ6⁺ γδT cells from skin colonized mice, marked by changes in tissue-residency and migration-associated genes. Lymphatic trafficking, proliferation and long-term recirculation sustain this response. These findings provide the first evidence that a localized commensal skin microbe can robustly reshape systemic γδT17 cell populations, with potentially distal functional consequences, offering new insights into how skin commensals dynamically tune allostatic setpoints. This hitherto unrecognized allostatic process by which discrete skin microbial signals can systemically recalibrate tissue IL-17 landscape and may represent a novel modality for harnessing microbiome-mediated γδT17 cells in treating metabolic, infectious, and inflammatory diseases."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Doctor of Philosophy (PhD)"]},{"key":"dc:title","label":"Title","values":["SKIN COMMENSAL STAPHYLOCOCCUS PROMOTES SYSTEMIC V-GAMMA-6 GAMMA-DELTA T CELL RECONFIGURATION"]}]}],"canonical_facts":{"dc:contributor.advisor":["Belkaid, Yasmine","Dang, Eric, V"],"dc:creator":["Rao, Indira, N"],"dc:date.accessioned":["2026-01-29T17:16:16Z"],"dc:date.available":["2026-01-29T17:16:16Z"],"dc:date.issued":["2025"],"dc:description":["2025"],"dc:description.abstract":["The gut microbiota is known to regulate both local immune responses and systemic functions in healthy hosts. However, it remains unclear whether the skin microbiota – resident on the body's largest barrier – can influence systemic responses. Skin-resident Staphylococcus aureus is a common commensal bacterium found in healthy individuals. This study demonstrates that, in mice, skin colonization by topical association with S. aureus reshapes systemic lymphocyte pools across lymphoid and non-lymphoid tissues. Notably, S. aureus skin colonization promotes a robust expansion of IL-17A-producing Vγ6⁺ γδT cells both locally in the dermis and systemically in lymphoid, mucosal, metabolic and central nervous system tissues. This systemic reconfiguration is IL-1R-dependent but independent of IL-23 receptor signaling and the endogenous microbiota. Transcriptomic profiling reveals a transitional state in dermal Vγ6⁺ γδT cells from skin colonized mice, marked by changes in tissue-residency and migration-associated genes. Lymphatic trafficking, proliferation and long-term recirculation sustain this response. These findings provide the first evidence that a localized commensal skin microbe can robustly reshape systemic γδT17 cell populations, with potentially distal functional consequences, offering new insights into how skin commensals dynamically tune allostatic setpoints. This hitherto unrecognized allostatic process by which discrete skin microbial signals can systemically recalibrate tissue IL-17 landscape and may represent a novel modality for harnessing microbiome-mediated γδT17 cells in treating metabolic, infectious, and inflammatory diseases."],"dc:description.degree":["Doctor of Philosophy (PhD)"],"dc:identifier.uri":["https://repository.upenn.edu/handle/20.500.14332/62257"],"dc:language.iso":["en"],"dc:subject":["Immunology and Infectious Disease","Biology"],"dc:title":["SKIN COMMENSAL STAPHYLOCOCCUS PROMOTES SYSTEMIC V-GAMMA-6 GAMMA-DELTA T CELL RECONFIGURATION"],"dc:type":["Dissertation/Thesis"]},"updated_at":"2026-07-24T03:45:38Z"}