Human pregnancy levels of estrogen and progesterone contribute to humoral immunity by activating TFH/B cell axis |
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Authors: | Clarice Monteiro Taissa Kasahara Priscila M Sacramento Aleida Dias Simone Leite Vander G Silva Sudhir Gupta Anshu Agrawal Cleonice A M Bento |
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Institution: | 1. Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
Post-graduate Program in Microbiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
These authors contributed equally to this work.;2. Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil;3. Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
Post-graduate Program in Microbiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil;4. Fernando Figueiras Institute, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil;5. Department of Medicine, University of California, Irvine, CA, USA |
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Abstract: | Circulating TFH (cTFH) cells express CXCR5, PD-1, and, when activated, ICOS, and release IL-21. According to the production of IFN-γ, IL-4, and IL-17 and expression of FoxP3, these cells are also classified as cTFH1, cTFH2, cTFH17, and cTFR cells, respectively. This CD4+T-cell subset is pivotal to efficient humoral immunity, and pregnancy appears to favor IgG production. Here, not only pregnancy amplified the in vivo production of anti-HBsAg IgG in HBV immunized women, but the frequency of cTFH cells was directly correlated with estradiol levels. In vitro, pregnancy-related dose of 17-β-estradiol (E2) directly increased the percentage of different cTFH subsets. While E2 and progesterone (P4) increased the proportion of differentiated TFH cells derived from naïve CD4+T-cells, only E2 amplified the release of IL-21 in those cell cultures. In addition, E2 and P4 increased the proportion of memory B cells and plasma cells, respectively. In SEB-activated B/TFH cell co-cultures, E2, in the presence of P4, increased the production of total IgG. Finally, among the hormones, P4 was stronger in upregulating the percentage of IL-10+TFR cells. Collectively, our findings suggested that E2 and P4 cooperate in the humoral immune response by favoring the expansion of different cTFH and B cell subsets. |
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Keywords: | anti-HBsAg IgG B cells estrogen progesterone TFH cells |
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