Systematic Immunophenotyping Reveals Sex-Specific Responses After Painful Injury in Mice
Many diseases display unequal prevalence between sexes. The sex-specific immune response to both injury and persistent pain remains underexplored and would inform treatment paradigms. We utilized high-dimensional mass cytometry to perform a comprehensive analysis of phenotypic and functional immune...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01652/full |
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| author | Vivianne L. Tawfik Nolan A. Huck Quentin J. Baca Edward A. Ganio Elena S. Haight Anthony Culos Sajjad Ghaemi Sajjad Ghaemi Thanaphong Phongpreecha Thanaphong Phongpreecha Thanaphong Phongpreecha Martin S. Angst J. David Clark Nima Aghaeepour Nima Aghaeepour Nima Aghaeepour Brice Gaudilliere Brice Gaudilliere |
| author_facet | Vivianne L. Tawfik Nolan A. Huck Quentin J. Baca Edward A. Ganio Elena S. Haight Anthony Culos Sajjad Ghaemi Sajjad Ghaemi Thanaphong Phongpreecha Thanaphong Phongpreecha Thanaphong Phongpreecha Martin S. Angst J. David Clark Nima Aghaeepour Nima Aghaeepour Nima Aghaeepour Brice Gaudilliere Brice Gaudilliere |
| author_sort | Vivianne L. Tawfik |
| collection | DOAJ |
| description | Many diseases display unequal prevalence between sexes. The sex-specific immune response to both injury and persistent pain remains underexplored and would inform treatment paradigms. We utilized high-dimensional mass cytometry to perform a comprehensive analysis of phenotypic and functional immune system differences between male and female mice after orthopedic injury. Multivariate modeling of innate and adaptive immune cell responses after injury using an elastic net algorithm, a regularized regression method, revealed sex-specific divergence at 12 h and 7 days after injury with a stronger immune response to injury in females. At 12 h, females upregulated STAT3 signaling in neutrophils but downregulated STAT1 and STAT6 signals in T regulatory cells, suggesting a lack of engagement of immune suppression pathways by females. Furthermore, at 7 days females upregulated MAPK pathways (p38, ERK, NFkB) in CD4T memory cells, setting up a possible heightened immune memory of painful injury. Taken together, our findings provide the first comprehensive and functional analysis of sex-differences in the immune response to painful injury. |
| first_indexed | 2024-12-21T01:28:06Z |
| format | Article |
| id | doaj.art-42e6d8e6c56645c2888e62a3a7e55c3c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T01:28:06Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-42e6d8e6c56645c2888e62a3a7e55c3c2022-12-21T19:20:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-07-011110.3389/fimmu.2020.01652557946Systematic Immunophenotyping Reveals Sex-Specific Responses After Painful Injury in MiceVivianne L. Tawfik0Nolan A. Huck1Quentin J. Baca2Edward A. Ganio3Elena S. Haight4Anthony Culos5Sajjad Ghaemi6Sajjad Ghaemi7Thanaphong Phongpreecha8Thanaphong Phongpreecha9Thanaphong Phongpreecha10Martin S. Angst11J. David Clark12Nima Aghaeepour13Nima Aghaeepour14Nima Aghaeepour15Brice Gaudilliere16Brice Gaudilliere17Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, United StatesDigital Technologies Research Centre, National Research Council Canada, Toronto, ON, CanadaDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, United StatesDepartment of Biomedical Data Sciences, Stanford University, Stanford, CA, United StatesDepartment of Pathology, Stanford University, Stanford, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, United StatesDepartment of Biomedical Data Sciences, Stanford University, Stanford, CA, United StatesDepartment of Pediatrics, Stanford University, Stanford, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, United StatesDepartment of Pediatrics, Stanford University, Stanford, CA, United StatesMany diseases display unequal prevalence between sexes. The sex-specific immune response to both injury and persistent pain remains underexplored and would inform treatment paradigms. We utilized high-dimensional mass cytometry to perform a comprehensive analysis of phenotypic and functional immune system differences between male and female mice after orthopedic injury. Multivariate modeling of innate and adaptive immune cell responses after injury using an elastic net algorithm, a regularized regression method, revealed sex-specific divergence at 12 h and 7 days after injury with a stronger immune response to injury in females. At 12 h, females upregulated STAT3 signaling in neutrophils but downregulated STAT1 and STAT6 signals in T regulatory cells, suggesting a lack of engagement of immune suppression pathways by females. Furthermore, at 7 days females upregulated MAPK pathways (p38, ERK, NFkB) in CD4T memory cells, setting up a possible heightened immune memory of painful injury. Taken together, our findings provide the first comprehensive and functional analysis of sex-differences in the immune response to painful injury.https://www.frontiersin.org/article/10.3389/fimmu.2020.01652/fullmass cytometryinjuryinflammationsex differencespainrecovery |
| spellingShingle | Vivianne L. Tawfik Nolan A. Huck Quentin J. Baca Edward A. Ganio Elena S. Haight Anthony Culos Sajjad Ghaemi Sajjad Ghaemi Thanaphong Phongpreecha Thanaphong Phongpreecha Thanaphong Phongpreecha Martin S. Angst J. David Clark Nima Aghaeepour Nima Aghaeepour Nima Aghaeepour Brice Gaudilliere Brice Gaudilliere Systematic Immunophenotyping Reveals Sex-Specific Responses After Painful Injury in Mice Frontiers in Immunology mass cytometry injury inflammation sex differences pain recovery |
| title | Systematic Immunophenotyping Reveals Sex-Specific Responses After Painful Injury in Mice |
| title_full | Systematic Immunophenotyping Reveals Sex-Specific Responses After Painful Injury in Mice |
| title_fullStr | Systematic Immunophenotyping Reveals Sex-Specific Responses After Painful Injury in Mice |
| title_full_unstemmed | Systematic Immunophenotyping Reveals Sex-Specific Responses After Painful Injury in Mice |
| title_short | Systematic Immunophenotyping Reveals Sex-Specific Responses After Painful Injury in Mice |
| title_sort | systematic immunophenotyping reveals sex specific responses after painful injury in mice |
| topic | mass cytometry injury inflammation sex differences pain recovery |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01652/full |
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