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Human pregnancy levels of estrogen and progesterone contribute to humoral immunity by activating T FH /B cell axis
Author(s) -
Monteiro Clarice,
Kasahara Taissa,
Sacramento Priscila M.,
Dias Aleida,
Leite Simone,
Silva Vander G.,
Gupta Sudhir,
Agrawal Anshu,
Bento Cleonice A. M.
Publication year - 2021
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.202048658
Subject(s) - biology , immune system , humoral immunity , medicine , estrogen , endocrinology , b cell , t cell , antibody , immunology
Abstract Circulating T FH (cT FH ) 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 cT FH 1, cT FH 2, cT FH 17, and cT FR 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 cT FH cells was directly correlated with estradiol levels. In vitro, pregnancy‐related dose of 17‐β‐estradiol (E2) directly increased the percentage of different cT FH subsets. While E2 and progesterone (P4) increased the proportion of differentiated T FH 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/T FH 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 + T FR cells. Collectively, our findings suggested that E2 and P4 cooperate in the humoral immune response by favoring the expansion of different cT FH and B cell subsets.