TY  - 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 .