The role of fungal-responsive CD1a-reactive T cells in the pathogenesis of atopic dermatitis
Atopic dermatitis (AD) is a common chronic inflammatory skin condition characterised by a skin-barrier defect, altered lipid profile and enrichment of CD1aexpressing antigen presenting cells. Although several endogenous epidermal CD1a ligands have been identified, non-endogenous ligands of CD1a are...
| প্রধান লেখক: | |
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| অন্যান্য লেখক: | |
| বিন্যাস: | গবেষণাপত্র |
| ভাষা: | English |
| প্রকাশিত: |
2019
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| বিষয়গুলি: |
| _version_ | 1826313012266401792 |
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| author | Ismaeel, A |
| author2 | Ogg, G |
| author_facet | Ogg, G Ismaeel, A |
| author_sort | Ismaeel, A |
| collection | OXFORD |
| description | Atopic dermatitis (AD) is a common chronic inflammatory skin condition characterised by a skin-barrier defect, altered lipid profile and enrichment of CD1aexpressing antigen presenting cells. Although several endogenous epidermal CD1a ligands have been identified, non-endogenous ligands of CD1a are still to be elucidated. There is an association between the presence of fungi such as C. albicans on the skin and AD pathogenesis, but no previous studies have investigated the specific role of fungal-responsive CD1a-reactive T cells. We hypothesised that AD is associated with an altered frequency and phenotype of fungal-responsive CD1a-reactive T cells in human blood and skin and that fungalresponsive CD1a-reactive T cells contribute to fungal immune responses, cutaneous immunity and AD. We tested this hypothesis by investigating the frequency and functional profile of fungal-responsive CD1a-reactive T cells in the blood and skin of healthy donors and patients with AD. We have shown that fungi may be sensed through the CD1a pathway through recognition of fungal lipids by CD1a-reactive T cells. We have characterised fungal-responsive CD1a-reactive T cell clones and identified their T cell receptor usage and co-receptor usage. Fungal antigens including unique fungal lipids such ergosterol and ergosterol esters and modified self-lipids such as squalene peroxide were identified to be possible novel CD1a-binding lipids. The fungal-responsive CD1a-reactive T cells may contribute to fungal defence and skin inflammation defining a broader understanding of the mechanisms underlying AD which will likely help in the design of novel therapeutics in the future. |
| first_indexed | 2024-03-07T05:02:45Z |
| format | Thesis |
| id | oxford-uuid:d8dd34b7-a7ad-49fb-973b-b97644a6ca02 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:04:13Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | oxford-uuid:d8dd34b7-a7ad-49fb-973b-b97644a6ca022024-05-15T07:57:40ZThe role of fungal-responsive CD1a-reactive T cells in the pathogenesis of atopic dermatitisThesishttp://purl.org/coar/resource_type/c_db06uuid:d8dd34b7-a7ad-49fb-973b-b97644a6ca02MycologyImmunologyDermatologyEnglishORA Deposit2019Ismaeel, AOgg, GXue, LAtopic dermatitis (AD) is a common chronic inflammatory skin condition characterised by a skin-barrier defect, altered lipid profile and enrichment of CD1aexpressing antigen presenting cells. Although several endogenous epidermal CD1a ligands have been identified, non-endogenous ligands of CD1a are still to be elucidated. There is an association between the presence of fungi such as C. albicans on the skin and AD pathogenesis, but no previous studies have investigated the specific role of fungal-responsive CD1a-reactive T cells. We hypothesised that AD is associated with an altered frequency and phenotype of fungal-responsive CD1a-reactive T cells in human blood and skin and that fungalresponsive CD1a-reactive T cells contribute to fungal immune responses, cutaneous immunity and AD. We tested this hypothesis by investigating the frequency and functional profile of fungal-responsive CD1a-reactive T cells in the blood and skin of healthy donors and patients with AD. We have shown that fungi may be sensed through the CD1a pathway through recognition of fungal lipids by CD1a-reactive T cells. We have characterised fungal-responsive CD1a-reactive T cell clones and identified their T cell receptor usage and co-receptor usage. Fungal antigens including unique fungal lipids such ergosterol and ergosterol esters and modified self-lipids such as squalene peroxide were identified to be possible novel CD1a-binding lipids. The fungal-responsive CD1a-reactive T cells may contribute to fungal defence and skin inflammation defining a broader understanding of the mechanisms underlying AD which will likely help in the design of novel therapeutics in the future. |
| spellingShingle | Mycology Immunology Dermatology Ismaeel, A The role of fungal-responsive CD1a-reactive T cells in the pathogenesis of atopic dermatitis |
| title | The role of fungal-responsive CD1a-reactive T cells in the pathogenesis of atopic dermatitis |
| title_full | The role of fungal-responsive CD1a-reactive T cells in the pathogenesis of atopic dermatitis |
| title_fullStr | The role of fungal-responsive CD1a-reactive T cells in the pathogenesis of atopic dermatitis |
| title_full_unstemmed | The role of fungal-responsive CD1a-reactive T cells in the pathogenesis of atopic dermatitis |
| title_short | The role of fungal-responsive CD1a-reactive T cells in the pathogenesis of atopic dermatitis |
| title_sort | role of fungal responsive cd1a reactive t cells in the pathogenesis of atopic dermatitis |
| topic | Mycology Immunology Dermatology |
| work_keys_str_mv | AT ismaeela theroleoffungalresponsivecd1areactivetcellsinthepathogenesisofatopicdermatitis AT ismaeela roleoffungalresponsivecd1areactivetcellsinthepathogenesisofatopicdermatitis |