Prolactin Increases the Frequency of Follicular T Helper Cells with Enhanced IL21 Secretion and OX40 Expression in Lupus-Prone MRL/lpr Mice

Systemic lupus erythematosus is characterized by high levels of IgG class autoantibodies that contribute to the pathophysiology of the disease. The formation of these autoantibodies occurs in the germinal centers, where there is cooperation between follicular T helper cells (TFH) and autoreactive B cells. Prolactin has been reported to exacerbate the clinical manifestations of lupus by increasing autoantibody concentrations. The objective of this study was to characterize the participation of prolactin in the differentiation and activation of TFH cells, by performing in vivo and in vitro tests with lupus-prone mice, using flow cytometry and real-time PCR. We found that TFH cells express the long isoform of the prolactin receptor and promoted STAT3 phosphorylation. Receptor expression was higher in MRL/lpr mice and correlative with the manifestations of the disease. Although prolactin does not intervene in the differentiation of TFH cells, it does favor their activation by increasing the percentage of TFH OX40+ and TFH IL21+ cells, as well as leading to high serum concentrations of IL21. These results support a mechanism in which prolactin participates in the emergence of lupus by inducing overactive TFH cells and perhaps promoting dysfunctional germinal centers.

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The frequency of follicular T helper cells differs in acute and chronic neuroinflammation

Scientific Reports ◽

10.1038/s41598-020-77588-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Adalie Baniahmad ◽

Katharina Birkner ◽

Johanna Görg ◽

Julia Loos ◽

Frauke Zipp ◽

...

Keyword(s):

T Helper Cells ◽

Clinical Symptoms ◽

T Helper ◽

Tfh Cells ◽

Helper Cells ◽

Inflammatory Processes ◽

The Central Nervous System ◽

Follicular T Helper Cells ◽

The Impact

AbstractBeyond the major role of T cells in the pathogenesis of the autoimmune neuroinflammatory disorder multiple sclerosis (MS), recent studies have highlighted the impact of B cells on pathogenic inflammatory processes. Follicular T helper cells (Tfh) are essential for the promotion of B cell-driven immune responses. However, their role in MS and its murine model, experimental autoimmune encephalomyelitis (EAE), is poorly investigated. A first step to achieving a better understanding of the contribution of Tfh cells to the disease is the consideration of Tfh cell localization in relation to genetic background and EAE induction method. Here, we investigated the Tfh cell distribution during disease progression in disease relevant organs in three different EAE models. An increase of Tfh frequency in the central nervous system (CNS) was observed during peak of C57BL/6 J EAE, paralleling chronic disease activity, whereas in relapsing–remitting SJL EAE mice Tfh cell frequencies were increased during remission. Furthermore, transferred Tfh-skewed cells polarized in vitro induced mild clinical symptoms in B6.Rag1−/− mice. We identified significantly higher levels of Tfh cells in the dura mater than in the CNS both in C57BL/6 and in SJL/J mice. Overall, our study emphasizes diverse, non-static roles of Tfh cells during autoimmune neuroinflammation.

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