The effect of sex on immune responses to a homocitrullinated peptide in the DR4-transgenic mouse model of Rheumatoid Arthritis
Autor: | Patrick Lac, Lillian Barra, Garth Blackler, David A. Bell, Sheri Saunders, Ewa Cairns |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Genetically modified mouse
lcsh:Immunologic diseases. Allergy Research paper medicine.medical_treatment T cell anti-CarP anti-carbamylated protein antibodies Immunology RA rheumatoid arthritis Biology Mouse model 03 medical and health sciences 0302 clinical medicine Immune system Antigen Anti-citrullinated protein/peptide antibodies HomoCitFib homocitrullinated fibrinogen Shared epitope Medicine and Health Sciences medicine Splenocyte Immunology and Allergy sc subcutaneous Rheumatoid arthritis 030304 developmental biology 030203 arthritis & rheumatology 0303 health sciences AHCPA anti-homocitrullinated protein/peptide antibodies Autoantibody medicine.disease Anti-homocitrullinated (carbamylated) protein/peptide antibodies ACPA anti-citrullinated protein/peptide antibodies ConA Concanavalin A SI stimulation index Cytokine medicine.anatomical_structure Cytokines Sex RF rheumatoid factor lcsh:RC581-607 |
Zdroj: | Journal of Translational Autoimmunity Journal of Translational Autoimmunity, Vol 3, Iss, Pp 100053-(2020) Bone and Joint Institute |
ISSN: | 2589-9090 |
Popis: | Rheumatoid Arthritis (RA) is more common and severe in women compared to men. Both women and men with RA express autoantibodies to post-translationally modified antigens, including citrullinated and homocitrullinated proteins or peptides. These autoantibodies are strongly linked with the HLA-DR4 gene. The objective of this study was to determine sex differences in immune responses to homocitrullinated antigens. We used a humanized animal model of RA, DR4-transgenic mice and immunized them with a homocitrullinated peptide called HomoCitJED. Immune responses in these mice were measured for splenocyte proliferation by tritiated thymidine incorporation, serum autoantibody production by ELISA and cytokine levels by multiplex. We found that T cell and antibody responses to homocitrullinated antigens were similar in male and female mice. However, we found sex differences in serum cytokine profiles with female mice having higher ratio of IL-1α to IL-5, suggesting imbalances in immune regulation. This is the first study to report that immune responses to homocitrullinated antigens can be differentiated by sex. Highlights • Splenocyte proliferation and antibody responses in DR4tg mice immunized with a homocitrullinated peptide were similar for females and males. • The cytokine profile of homocitrullinated peptide-immunized DR4tg mice was differentiated by sex: females had a higher ratio of IL-1α to IL-5. • Anti-homocitrullinated peptide splenocyte and antibody responses were more frequent in DR4tg than wild-type B6 mice. |
Databáze: | OpenAIRE |
Externí odkaz: |