Prolactin Is Not Required for the Development of Severe Chronic Experimental Autoimmune Encephalomyelitis

Abstract

Predominance of multiple sclerosis (MS) in women, reductions of disease flares during pregnancy, and their increase in the postpartum period have suggested a hormonal influence on MS activity. The hormone prolactin (PRL) has long been debated as a potential immune-stimulating factor in several autoimmune disorders, including MS and its animal model experimental autoimmune encephalomyelitis (EAE). However, to date, no data clearly ascribe a pathogenic role to PRL in these diseases. Using PRL receptor–deficient (Prlr−/−) and PRL-deficient (Prl−/−) mice, we show that PRL plays a redundant role in the development of chronic EAE. In Prlr−/− and Prl−/− mice, EAE developed with a delayed onset compared with littermate control mice, but with full clinical severity. In line with the clinical outcome, T cell proliferation and production of IFN-γ, IL-17A, and IL-6 induced by myelin Ag were delayed in Prlr−/− and Prl−/− mice. Ag-specific IgG Ab responses were not affected by PRLR or PRL deficiency. We also show that mouse lymph node cells and purified CD4+ T cells express transcript for Prlr, but not for Prl. These results reveal that PRL does not play a central role in the development of chronic EAE and optimal Th1 and Th17 responses against myelin. Moreover, they also rule out a possible contribution of PRL secreted by immune cells to the modulation of autoreactive T cell response in this model.

Prolactin: A versatile regulator of inflammation and autoimmune pathology

“…In line with these data, we did not detect PRL at either mRNA or protein levels in mouse primary CD4 + T cells [35]. In human T cells, PRL has been proposed to support proliferation [36], survival [37], and to act as an autocrine factor.…”

“…16 [35]. These findings appear to rule out CD4 + T cells as a possible source of local PRL that could contribute in an autocrine manner to the development of autoreactive T cell responses in EAE.…”

“…This study has suggested that PRL does not impact crucially on EAE expression [35]. Indeed, PRL and PRLR-deficient mice develop EAE with a slightly delayed onset compared to littermate control mice but with full clinical severity.…”

Prolactin: Friend or Foe in Central Nervous System Autoimmune Inflammation?

“…PRL has been proposed as an autocrine factor sustaining survival and proliferation of human T cells [35,36]. On the contrary, no Prl transcript or protein have been detected in purified CD4 + T cell cultures of mouse origin [37]. In this regard, it is important to consider that a single promoter drives Prl expression in rodents, while an additional “extra-pituitary” promoter has been described in humans [38].…”

“…Others and we have recently characterized the development of chronic EAE in Prlr −/− and Prl −/− mice, elicited by immunization with MOG peptide 35–55 (MOG 35–55 ). We reported that mice lacking PRLR or PRL develop chronic EAE with a modestly but significantly delayed onset and a disease severity comparable to control mice [37]. The retardation in the presentation of clinical symptoms observed in Prlr −/− and Prl −/− mice is associated with a mild delay in the development of Th1 and Th17 autoimmune responses against myelin in draining lymph nodes [37].…”