RESUMO
The HLA-B*40:538 allele differs from HLA-B*40:01:02:01 at position 905 CâT in exon 5.
Assuntos
Genes MHC Classe I , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Alelos , Éxons/genética , Antígenos HLA-B/genéticaRESUMO
The novel HLA-B*35:502 allele differs from HLA-B*35:01:01:01 at one position in exon 2.
Assuntos
Genes MHC Classe I , Antígenos HLA-B , Humanos , Alelos , Éxons/genética , Antígenos HLA-B/genética , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
Bariatric surgery is currently the most effective strategy in treating severe obesity and its comorbidities, such as type 2 diabetes (T2D). However, the mechanism through which bariatric surgery mediates its benefits is not completely understood. Since obesity and T2D represent yet another inflammatory disease, and follicular helper T (Tfh) cells play important roles in inflammatory disorders, we investigated whether the Tfh activity was altered after Roux-en-Y gastric bypass (RYGB), one of the most common bariatric surgery procedures. We found that the Tfh cells after RYGB were not significantly changed in number, but presented altered cytokine secretion profile, including lower interferon (IFN)-γ, interleukin (IL)-2, IL-4, and IL-17 secretion. Tfh cells after RYGB also downregulated inducible co-stimulator and programmed death-1. Interestingly, after Tfh cell-naive B cell coculture, Tfh cells after RYGB secreted more IL-10 than autologous Tfh cells before RYGB. The frequencies of IL-10-expressing and transforming growth factor (TGF)-ß-expressing regulatory B cells after Tfh cell-naive B cell coculture were directly correlated with the frequency of IL-10-expressing Tfh cells. Depletion of IL-10 in the coculture, however, resulted in fewer regulatory B cells. Finally, patients with greater increase in IL-10-expressing Tfh cells presented further reductions in body mass index, glycaemia, and body fat percentage. Together, these data demonstrated that the Tfh cells after RYGB presented lower inflammatory status and secreted higher IL-10, through which these Tfh cells promoted the development of regulatory B cells. Higher IL-10-expressing Tfh cell level also predicted better patient response to RYGB.
