Sexual dimorphism in the severity of rat collagen-induced arthritis: The relevance of T follicular cell help to B cells
Аутори
Dimitrijević, MirjanaArsenović-Ranin, Nevena
Kosec, Duško
Bufan, Biljana
Nacka-Aleksić, Mirjana
Pilipović, Ivan
Leposavić, Gordana
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Collagen-induced arthritis (CIA) is a well-established experimental model mimicking
many immunopathogenic and clinical aspects of rheumatoid arthritis (RA), including
sexual dimorphism in the clinical presentation. Our previous study showed that a more
severe disease in female compared with male rats correlated with more robust Th17
response reflecting sexual dimorphism in Th17/Treg axis plasticity. Given that
autoantibodies play a significant role in the immunopathogenesis of RA and CIA, in
the present study the germinal center (GC) reaction in the lymph nodes draining
inflamed joints and adjacent tissue (dLNs) was examined for putative sexual
dimorphism. Female rats mounted greater serum collagen II-specific IgG response than
their male counterparts. This dimorphism correlated with the higher frequency of GC
B cells in female compared with male dLNs. Consistently, the frequency of
activated/proliferating Ki67+ cells among dLN B cells was higher in females than i...n
males. This was associated with the shift in dLN T follicular regulatory (Tfr)/T
follicular helper (Tfh) cell ratio towards Tfh cells in females, and greater densities of
CD40L and CD40 on their dLN T and B cells, respectively. The higher Tfh cell
frequency in females was consistent with the greater dLN expression of mRNA for IL 21/27, the key cytokines involved in Tfh cell generation and help to B cells.
Additionally, in collagen II-stimulated female rat dLN cell cultures, IFN-γ/IL-4 ratio
was shifted towards IFN-γ. Consistently, serum ratio between pathogenic IgG2a and
protective IgG1 collagen II-specific antibodies was shifted towards the former in
females. Thus, the study suggests that targeting T/B cell interactions should be
considered in further translation research aimed to design sex-specific therapies for RA.
Извор:
Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8. 2019, Abstract book, 2019Издавач:
- Institute for Biological Research "Siniša Stanković" National Institute of Republic of Serbia
- Immunological Society of Serbia
Финансирање / пројекти:
- Пластичност имунског система током старења: имуномодулаторни потенцијал естрогена (RS-MESTD-Basic Research (BR or ON)-175050)
Институција/група
PharmacyTY - CONF AU - Dimitrijević, Mirjana AU - Arsenović-Ranin, Nevena AU - Kosec, Duško AU - Bufan, Biljana AU - Nacka-Aleksić, Mirjana AU - Pilipović, Ivan AU - Leposavić, Gordana PY - 2019 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5087 AB - Collagen-induced arthritis (CIA) is a well-established experimental model mimicking many immunopathogenic and clinical aspects of rheumatoid arthritis (RA), including sexual dimorphism in the clinical presentation. Our previous study showed that a more severe disease in female compared with male rats correlated with more robust Th17 response reflecting sexual dimorphism in Th17/Treg axis plasticity. Given that autoantibodies play a significant role in the immunopathogenesis of RA and CIA, in the present study the germinal center (GC) reaction in the lymph nodes draining inflamed joints and adjacent tissue (dLNs) was examined for putative sexual dimorphism. Female rats mounted greater serum collagen II-specific IgG response than their male counterparts. This dimorphism correlated with the higher frequency of GC B cells in female compared with male dLNs. Consistently, the frequency of activated/proliferating Ki67+ cells among dLN B cells was higher in females than in males. This was associated with the shift in dLN T follicular regulatory (Tfr)/T follicular helper (Tfh) cell ratio towards Tfh cells in females, and greater densities of CD40L and CD40 on their dLN T and B cells, respectively. The higher Tfh cell frequency in females was consistent with the greater dLN expression of mRNA for IL 21/27, the key cytokines involved in Tfh cell generation and help to B cells. Additionally, in collagen II-stimulated female rat dLN cell cultures, IFN-γ/IL-4 ratio was shifted towards IFN-γ. Consistently, serum ratio between pathogenic IgG2a and protective IgG1 collagen II-specific antibodies was shifted towards the former in females. Thus, the study suggests that targeting T/B cell interactions should be considered in further translation research aimed to design sex-specific therapies for RA. PB - Institute for Biological Research "Siniša Stanković" National Institute of Republic of Serbia PB - Immunological Society of Serbia C3 - Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8. 2019, Abstract book T1 - Sexual dimorphism in the severity of rat collagen-induced arthritis: The relevance of T follicular cell help to B cells UR - https://hdl.handle.net/21.15107/rcub_farfar_5087 ER -
@conference{ author = "Dimitrijević, Mirjana and Arsenović-Ranin, Nevena and Kosec, Duško and Bufan, Biljana and Nacka-Aleksić, Mirjana and Pilipović, Ivan and Leposavić, Gordana", year = "2019", abstract = "Collagen-induced arthritis (CIA) is a well-established experimental model mimicking many immunopathogenic and clinical aspects of rheumatoid arthritis (RA), including sexual dimorphism in the clinical presentation. Our previous study showed that a more severe disease in female compared with male rats correlated with more robust Th17 response reflecting sexual dimorphism in Th17/Treg axis plasticity. Given that autoantibodies play a significant role in the immunopathogenesis of RA and CIA, in the present study the germinal center (GC) reaction in the lymph nodes draining inflamed joints and adjacent tissue (dLNs) was examined for putative sexual dimorphism. Female rats mounted greater serum collagen II-specific IgG response than their male counterparts. This dimorphism correlated with the higher frequency of GC B cells in female compared with male dLNs. Consistently, the frequency of activated/proliferating Ki67+ cells among dLN B cells was higher in females than in males. This was associated with the shift in dLN T follicular regulatory (Tfr)/T follicular helper (Tfh) cell ratio towards Tfh cells in females, and greater densities of CD40L and CD40 on their dLN T and B cells, respectively. The higher Tfh cell frequency in females was consistent with the greater dLN expression of mRNA for IL 21/27, the key cytokines involved in Tfh cell generation and help to B cells. Additionally, in collagen II-stimulated female rat dLN cell cultures, IFN-γ/IL-4 ratio was shifted towards IFN-γ. Consistently, serum ratio between pathogenic IgG2a and protective IgG1 collagen II-specific antibodies was shifted towards the former in females. Thus, the study suggests that targeting T/B cell interactions should be considered in further translation research aimed to design sex-specific therapies for RA.", publisher = "Institute for Biological Research "Siniša Stanković" National Institute of Republic of Serbia, Immunological Society of Serbia", journal = "Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8. 2019, Abstract book", title = "Sexual dimorphism in the severity of rat collagen-induced arthritis: The relevance of T follicular cell help to B cells", url = "https://hdl.handle.net/21.15107/rcub_farfar_5087" }
Dimitrijević, M., Arsenović-Ranin, N., Kosec, D., Bufan, B., Nacka-Aleksić, M., Pilipović, I.,& Leposavić, G.. (2019). Sexual dimorphism in the severity of rat collagen-induced arthritis: The relevance of T follicular cell help to B cells. in Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8. 2019, Abstract book Institute for Biological Research "Siniša Stanković" National Institute of Republic of Serbia.. https://hdl.handle.net/21.15107/rcub_farfar_5087
Dimitrijević M, Arsenović-Ranin N, Kosec D, Bufan B, Nacka-Aleksić M, Pilipović I, Leposavić G. Sexual dimorphism in the severity of rat collagen-induced arthritis: The relevance of T follicular cell help to B cells. in Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8. 2019, Abstract book. 2019;. https://hdl.handle.net/21.15107/rcub_farfar_5087 .
Dimitrijević, Mirjana, Arsenović-Ranin, Nevena, Kosec, Duško, Bufan, Biljana, Nacka-Aleksić, Mirjana, Pilipović, Ivan, Leposavić, Gordana, "Sexual dimorphism in the severity of rat collagen-induced arthritis: The relevance of T follicular cell help to B cells" in Immunology at the confluence of multidisciplinary approaces, Belgrade December 6.-8. 2019, Abstract book (2019), https://hdl.handle.net/21.15107/rcub_farfar_5087 .