Sex and Pubertal Differences in the Type 1 Interferon Pathway Associate With Both X Chromosome Number and Serum Sex Hormone Concentration
Type 1 interferons (IFN) are an antiviral cytokine family, important in juvenile onset systemic lupus erythematosus (jSLE) which is more common in females, around puberty. We report that plasmacytoid dendritic cells (pDC) from healthy females produced more type 1 IFN after toll like receptor (TLR) 7...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-01-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.03167/full |
| _version_ | 1828739617405272064 |
|---|---|
| author | Kate Webb Hannah Peckham Anna Radziszewska Madhvi Menon Paola Oliveri Fraser Simpson Claire T. Deakin Claire T. Deakin Claire T. Deakin Sophie Lee Coziana Ciurtin Gary Butler Gary Butler Lucy R. Wedderburn Lucy R. Wedderburn Lucy R. Wedderburn Yiannis Ioannou |
| author_facet | Kate Webb Hannah Peckham Anna Radziszewska Madhvi Menon Paola Oliveri Fraser Simpson Claire T. Deakin Claire T. Deakin Claire T. Deakin Sophie Lee Coziana Ciurtin Gary Butler Gary Butler Lucy R. Wedderburn Lucy R. Wedderburn Lucy R. Wedderburn Yiannis Ioannou |
| author_sort | Kate Webb |
| collection | DOAJ |
| description | Type 1 interferons (IFN) are an antiviral cytokine family, important in juvenile onset systemic lupus erythematosus (jSLE) which is more common in females, around puberty. We report that plasmacytoid dendritic cells (pDC) from healthy females produced more type 1 IFN after toll like receptor (TLR) 7 signaling than males, even before puberty, but that puberty itself associated with increased production of type 1 IFN. A unique human model allows us to show that this was related to X chromosome number, and serum testosterone concentration, in a manner which differed depending on the number of X chromosomes present. In addition, we have showed that pDC were more activated in females overall, and immune cell TLR7 gene expression was higher in females after puberty. Therefore, sex hormones and X chromosome number were associated individually and interactively with the type 1 IFN response, which contributes to our understanding of why females are more likely to develop an IFN mediated disease like jSLE after puberty. |
| first_indexed | 2024-04-13T00:25:33Z |
| format | Article |
| id | doaj.art-4b90538d62b849ac83fc847d78e95bd9 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T00:25:33Z |
| publishDate | 2019-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4b90538d62b849ac83fc847d78e95bd92022-12-22T03:10:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-01-01910.3389/fimmu.2018.03167429464Sex and Pubertal Differences in the Type 1 Interferon Pathway Associate With Both X Chromosome Number and Serum Sex Hormone ConcentrationKate Webb0Hannah Peckham1Anna Radziszewska2Madhvi Menon3Paola Oliveri4Fraser Simpson5Claire T. Deakin6Claire T. Deakin7Claire T. Deakin8Sophie Lee9Coziana Ciurtin10Gary Butler11Gary Butler12Lucy R. Wedderburn13Lucy R. Wedderburn14Lucy R. Wedderburn15Yiannis Ioannou16Arthritis Research UK Centre for Adolescent Rheumatology at UCL, ULCH and GOSH, London, United KingdomArthritis Research UK Centre for Adolescent Rheumatology at UCL, ULCH and GOSH, London, United KingdomArthritis Research UK Centre for Adolescent Rheumatology at UCL, ULCH and GOSH, London, United KingdomDivision of Medicine, Centre for Rheumatology, UCL, London, United KingdomDepartment of Genetics, Evolution and Environment, Nanostring Facility, UCL, London, United KingdomDepartment of Genetics, Evolution and Environment, Nanostring Facility, UCL, London, United KingdomArthritis Research UK Centre for Adolescent Rheumatology at UCL, ULCH and GOSH, London, United KingdomNIHR Biomedical Research Centre at GOSH, London, United KingdomIII Programme UCL GOS Institute for Child Health, London, United KingdomCentre for Applied Statistics Courses, Great Ormond Street Institute of Child Health, UCL, London, United KingdomArthritis Research UK Centre for Adolescent Rheumatology at UCL, ULCH and GOSH, London, United KingdomDepartment of Paediatric and Adolescent Endocrinology, UCLH and Great Ormond Street Institute of Child Health, UCL, London, United KingdomGender Identity Development Service (GIDS), Tavistock and Portman NHS Foundation Trust, London, United KingdomArthritis Research UK Centre for Adolescent Rheumatology at UCL, ULCH and GOSH, London, United KingdomNIHR Biomedical Research Centre at GOSH, London, United KingdomIII Programme UCL GOS Institute for Child Health, London, United KingdomArthritis Research UK Centre for Adolescent Rheumatology at UCL, ULCH and GOSH, London, United KingdomType 1 interferons (IFN) are an antiviral cytokine family, important in juvenile onset systemic lupus erythematosus (jSLE) which is more common in females, around puberty. We report that plasmacytoid dendritic cells (pDC) from healthy females produced more type 1 IFN after toll like receptor (TLR) 7 signaling than males, even before puberty, but that puberty itself associated with increased production of type 1 IFN. A unique human model allows us to show that this was related to X chromosome number, and serum testosterone concentration, in a manner which differed depending on the number of X chromosomes present. In addition, we have showed that pDC were more activated in females overall, and immune cell TLR7 gene expression was higher in females after puberty. Therefore, sex hormones and X chromosome number were associated individually and interactively with the type 1 IFN response, which contributes to our understanding of why females are more likely to develop an IFN mediated disease like jSLE after puberty.https://www.frontiersin.org/article/10.3389/fimmu.2018.03167/fullinterferonTLR7immunitysexpubertySLE |
| spellingShingle | Kate Webb Hannah Peckham Anna Radziszewska Madhvi Menon Paola Oliveri Fraser Simpson Claire T. Deakin Claire T. Deakin Claire T. Deakin Sophie Lee Coziana Ciurtin Gary Butler Gary Butler Lucy R. Wedderburn Lucy R. Wedderburn Lucy R. Wedderburn Yiannis Ioannou Sex and Pubertal Differences in the Type 1 Interferon Pathway Associate With Both X Chromosome Number and Serum Sex Hormone Concentration Frontiers in Immunology interferon TLR7 immunity sex puberty SLE |
| title | Sex and Pubertal Differences in the Type 1 Interferon Pathway Associate With Both X Chromosome Number and Serum Sex Hormone Concentration |
| title_full | Sex and Pubertal Differences in the Type 1 Interferon Pathway Associate With Both X Chromosome Number and Serum Sex Hormone Concentration |
| title_fullStr | Sex and Pubertal Differences in the Type 1 Interferon Pathway Associate With Both X Chromosome Number and Serum Sex Hormone Concentration |
| title_full_unstemmed | Sex and Pubertal Differences in the Type 1 Interferon Pathway Associate With Both X Chromosome Number and Serum Sex Hormone Concentration |
| title_short | Sex and Pubertal Differences in the Type 1 Interferon Pathway Associate With Both X Chromosome Number and Serum Sex Hormone Concentration |
| title_sort | sex and pubertal differences in the type 1 interferon pathway associate with both x chromosome number and serum sex hormone concentration |
| topic | interferon TLR7 immunity sex puberty SLE |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.03167/full |
| work_keys_str_mv | AT katewebb sexandpubertaldifferencesinthetype1interferonpathwayassociatewithbothxchromosomenumberandserumsexhormoneconcentration AT hannahpeckham sexandpubertaldifferencesinthetype1interferonpathwayassociatewithbothxchromosomenumberandserumsexhormoneconcentration AT annaradziszewska sexandpubertaldifferencesinthetype1interferonpathwayassociatewithbothxchromosomenumberandserumsexhormoneconcentration AT madhvimenon sexandpubertaldifferencesinthetype1interferonpathwayassociatewithbothxchromosomenumberandserumsexhormoneconcentration AT paolaoliveri sexandpubertaldifferencesinthetype1interferonpathwayassociatewithbothxchromosomenumberandserumsexhormoneconcentration AT frasersimpson sexandpubertaldifferencesinthetype1interferonpathwayassociatewithbothxchromosomenumberandserumsexhormoneconcentration AT clairetdeakin sexandpubertaldifferencesinthetype1interferonpathwayassociatewithbothxchromosomenumberandserumsexhormoneconcentration AT clairetdeakin sexandpubertaldifferencesinthetype1interferonpathwayassociatewithbothxchromosomenumberandserumsexhormoneconcentration AT clairetdeakin sexandpubertaldifferencesinthetype1interferonpathwayassociatewithbothxchromosomenumberandserumsexhormoneconcentration AT sophielee sexandpubertaldifferencesinthetype1interferonpathwayassociatewithbothxchromosomenumberandserumsexhormoneconcentration AT cozianaciurtin sexandpubertaldifferencesinthetype1interferonpathwayassociatewithbothxchromosomenumberandserumsexhormoneconcentration AT garybutler sexandpubertaldifferencesinthetype1interferonpathwayassociatewithbothxchromosomenumberandserumsexhormoneconcentration AT garybutler sexandpubertaldifferencesinthetype1interferonpathwayassociatewithbothxchromosomenumberandserumsexhormoneconcentration AT lucyrwedderburn sexandpubertaldifferencesinthetype1interferonpathwayassociatewithbothxchromosomenumberandserumsexhormoneconcentration AT lucyrwedderburn sexandpubertaldifferencesinthetype1interferonpathwayassociatewithbothxchromosomenumberandserumsexhormoneconcentration AT lucyrwedderburn sexandpubertaldifferencesinthetype1interferonpathwayassociatewithbothxchromosomenumberandserumsexhormoneconcentration AT yiannisioannou sexandpubertaldifferencesinthetype1interferonpathwayassociatewithbothxchromosomenumberandserumsexhormoneconcentration |