Contribution of sex steroids and prolactin to the modulation of T and B cells during autoimmunity

Recalde, Gabriela; Moreno-Sosa, Tamara; Yúdica, Florencia; Quintero, Cristián; Sánchez, María Belén; Jahn, Graciela A.; Kalergis, Alexis M.; Mackern-Oberti, Juan Pablo

doi:10.1016/j.autrev.2018.03.006

Cited by 45 publications

(35 citation statements)

References 151 publications

(187 reference statements)

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“…Additionally, comparing to CD34 + PRLR − progenitors, CD34 + PRLR + progenitors expressed more PRL mRNA ( Fig. 6A), perhaps suggesting autocrine activity of this molecule in CD34 + PRLR + progenitors 26,27,44 . These and the above findings prompted us to investigate the transcriptional influence of PRL on the CD34 + PRLR + myeloid cells by adding human recombinant PRL into the cultures.…”

Section: Prlr-expressing Progenitors Are Derived From Gmps and Differmentioning

confidence: 94%

“…(B-F) Data are shown as means ± SD, One-way ANOVA erythroid progenitors from CD34 + cells 24,26 . PRL also drives the maturation and activation of T cells, B cells, NK cells, neutrophils, macrophages and dendritic cells [27][28][29][30][31][32][33] . This hormone is released mainly by the anterior pituitary gland, although immune cells, such as myeloid cells, are non-endocrine sources of PRL 27,28,34,35 .…”

mentioning

confidence: 99%

“…PRL also drives the maturation and activation of T cells, B cells, NK cells, neutrophils, macrophages and dendritic cells [27][28][29][30][31][32][33] . This hormone is released mainly by the anterior pituitary gland, although immune cells, such as myeloid cells, are non-endocrine sources of PRL 27,28,34,35 . PRL signals through the PRL receptor (PRLR), which is a member of the cytokine receptor superfamily [36][37][38][39][40] because of its use of kinases and signal transduction activators of transcription (STATs) 36,38,41 .…”

mentioning

confidence: 99%

“…PRL signals through the PRL receptor (PRLR), which is a member of the cytokine receptor superfamily [36][37][38][39][40] because of its use of kinases and signal transduction activators of transcription (STATs) 36,38,41 . Apart from mammary gland tissue, decidua and uterus all of which abundantly express PRLR, immune cells also express this receptor 27,34,39,42,43 . Moreover, myeloid cells can co-express both PRL and its receptor (PRLR), indicating the existence of both autocrine and paracrine actions of this molecule within the hematopoietic system 26,27,34,44 .…”

mentioning

confidence: 99%

“…Apart from mammary gland tissue, decidua and uterus all of which abundantly express PRLR, immune cells also express this receptor 27,34,39,42,43 . Moreover, myeloid cells can co-express both PRL and its receptor (PRLR), indicating the existence of both autocrine and paracrine actions of this molecule within the hematopoietic system 26,27,34,44 .…”

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confidence: 99%

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Prolactin Acts on Myeloid Progenitors to Modulate SMAD7 Expression and Enhance Hematopoietic Stem Cell Differentiation into the NK Cell Lineage

Tufa

Shank

Yingst

et al. 2020

Sci Rep

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Numerous cell types modulate hematopoiesis through soluble and membrane bound molecules. Whether developing hematopoietic progenitors of a particular lineage modulate the differentiation of other hematopoietic lineages is largely unknown. Here we aimed to investigate the influence of myeloid progenitors on CD34 + cell differentiation into CD56 + innate lymphocytes. Sorted CD34 + cells cultured in the presence of stem cell factor (SCF) and FMS-like tyrosine kinase 3 ligand (FLT3L) give rise to numerous cell types, including progenitors that expressed the prolactin receptor (PRLR). These CD34 + pRLR + myeloid-lineage progenitors were derived from granulocyte monocyte precursors (GMPs) and could develop into granulocytes in the presence of granulocyte-macrophage colonystimulating factor (GM-CSF) in vitro. Moreover, CD34 + pRLR + myeloid progenitors lacked lymphoid developmental potential, but when stimulated with prolactin (PRL) they increased the differentiation of other CD34 + cell populations into the NK lineage in a non-contact dependent manner. Both mRNA and protein analyses show that PRL increased mothers against decapentaplegic homolog 7 (SMAD7) in CD34 + pRLR + myeloid cells, which reduced the production of transforming growth factor beta 1 (TGF-β1), a cytokine known to inhibit CD56 + cell development. Thus, we uncover an axis whereby CD34 + pRLR + GMPs inhibit CD56 + lineage development through TGF-β1 production and PRL stimulation leads to SMAD7 activation, repression of TGF-β1, resulting in CD56 + cell development. Hematopoietic differentiation is specified by a multitude of soluble and membrane-bound molecules produced both within and outside of the hematopoietic system that influence cell fate decisions 1-6. In line with this, numerous cytokines including interleukin (IL)-1, IL-2, IL-7, IL-12, IL-15, IL-18, IL-21, IL-23, IL-25 and IL-33 have been shown to modulate the development of NK cells and other innate lymphoid cells (ILCs) 7-14. Moreover, NK cells and other ILCs require different transcription factors such as Tbet, RORc and Gata3 for their development 7,15,16. Multi-lymphoid progenitor (MLP) differentiate into the common ILC progenitor and this cell then gives rise to NK cells and all helper ILCs (i.e., ILC1, 2 and 3) 12-14,17. NK cells and helper ILCs are distinguished by specific transcription factor expression, cytokine production and function 9,13,14,18,19. We have used in vitro differentiation to study these processes and over the last decade have found that both NK cells and helper ILCs (particularly, ILC1s and ILC3s) develop in this system and similarly express CD56 16,20-23. Therefore, throughout this manuscript we use the term CD56 + lymphocytes to describe all CD56 expressing cells. Prolactin (PRL) is a neuroendocrine hormone best known for its role in lactation. However, PRL also regulates hematopoietic cell development and homeostasis 24-28. Specifically, PRL enhances the development of myeloid and

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Section: Prlr-expressing Progenitors Are Derived From Gmps and Differmentioning

confidence: 94%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Prolactin Acts on Myeloid Progenitors to Modulate SMAD7 Expression and Enhance Hematopoietic Stem Cell Differentiation into the NK Cell Lineage

Tufa

Shank

Yingst

et al. 2020

Sci Rep

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Human pregnancy levels of estrogen and progesterone contribute to humoral immunity by activating T_FH/B cell axis

et al. 2020

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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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Comprehensive approach for identification of functional FCGR2C alleles resulting in protein expression as a determinant for predicting predisposition to autoimmunity

et al. 2021

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The balance of activating and inhibitory signals from the low affinity Fc gamma receptors modulates immune responses triggered by IgG antibody-immune complexes.In homeostasis, this leads to antigen clearance, while in autoimmune diseases to unwanted immune response. Besides the activating receptors FcɣRIIa, FcɣRIIIa, and the inhibitory FcɣRIIb receptor, a third activating receptor, FcɣRIIc, was shown to be expressed on several immune cell types, however, only in the presence of a functional FCGR2C-ORF allele. FcɣRIIc expression is associated with autoimmune diseases such as idiopathic thrombocytopenic purpura, systemic lupus erythematosus or systemic sclerosis. Thus, the determination of the functional FCGR2C gene resulting in protein expression on immune cells becomes highly relevant, particularly in the context of unwanted immune responses through inadvertent FcɣRIIc activation by molecules targeting stimulation of the inhibitory receptor FcɣRIIb, currently pursued by several pharmaceutical companies. The high degree of homology within the FCGR2/3 gene cluster complicates development of an accurate method for identification of FcɣRIIc expression. Here we describe a comprehensive approach to characterize genetic status of the FCGR2C gene locus consisting of cDNA sequencing, SNaPshot genotyping and low-coverage next-generation sequencing. This might enable Mendelian randomization hypothesis testing across autoimmune diseases to personalize therapies and enhance treatment outcomes.

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Contribution of sex steroids and prolactin to the modulation of T and B cells during autoimmunity

Cited by 45 publications

References 151 publications

Prolactin Acts on Myeloid Progenitors to Modulate SMAD7 Expression and Enhance Hematopoietic Stem Cell Differentiation into the NK Cell Lineage

Prolactin Acts on Myeloid Progenitors to Modulate SMAD7 Expression and Enhance Hematopoietic Stem Cell Differentiation into the NK Cell Lineage

Human pregnancy levels of estrogen and progesterone contribute to humoral immunity by activating T_FH/B cell axis

Comprehensive approach for identification of functional FCGR2C alleles resulting in protein expression as a determinant for predicting predisposition to autoimmunity

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Contribution of sex steroids and prolactin to the modulation of T and B cells during autoimmunity

Cited by 45 publications

References 151 publications

Prolactin Acts on Myeloid Progenitors to Modulate SMAD7 Expression and Enhance Hematopoietic Stem Cell Differentiation into the NK Cell Lineage

Prolactin Acts on Myeloid Progenitors to Modulate SMAD7 Expression and Enhance Hematopoietic Stem Cell Differentiation into the NK Cell Lineage

Human pregnancy levels of estrogen and progesterone contribute to humoral immunity by activating TFH/B cell axis

Comprehensive approach for identification of functional FCGR2C alleles resulting in protein expression as a determinant for predicting predisposition to autoimmunity

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Human pregnancy levels of estrogen and progesterone contribute to humoral immunity by activating T_FH/B cell axis