Prolactin down-regulates CD4+CD25hiCD127low/− regulatory T cell function in humans

Abstract

Among its many functions, prolactin (PRL) participates in immune responses and promotes the activation, differentiation and proliferation of T cells. However, the mechanisms by which PRL regulates regulatory T (T reg ) cells are still unknown. Our goal was to determine whether PRL plays a role in T reg function. We measured the expression of PRL and its receptor in T reg and effector T (T eff ) cells from 15 healthy individuals. We also evaluated the functional activity of T reg cells by examining proliferation and cytokine secretion in cells activated with anti-CD3/CD28 in the presence or absence of PRL. We report that T reg cells constitutively expressed PRL receptor, whereas T eff cells required stimulation with anti-CD3/CD28 to induce PRL receptor expression. Expression of PRL was constitutive in both populations. We found that the addition of PRL inhibited the suppressor effect (proliferation) mediated by T reg cells in vitro, reducing suppression from 37 . 4 to 13% when PRL was added to co-cultures of T reg and T eff cells (P!0 . 05). Cultures treated with PRL favoured a Th1 cytokine profile, with increased production of TNF and IFNg. We report for the first time that PRL receptor expression was constitutive in T reg cells but not in T eff cells, which require stimulation to induce PRL receptor expression. PRL inhibited the suppressive function of T reg cells, apparently through the induced secretion of Th1 cytokines.

Prolactin Variants in Human Pituitaries and Pituitary Adenomas Identified With Two-Dimensional Gel Electrophoresis and Mass Spectrometry

“…PRL has different functions in the immune system of healthy people, including Treg cell inhibitory factor and inhibition of cell secretion (45). PRL contributes to the inflammatory microenvironment by reducing the inhibitory effect of Treg cells on T cells (45, 46). The proteolytic fragments of native PRL inhibit angiogenesis.…”

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

“…Regulatory T cells (Treg) represent a T cell subset with immune-suppressive functions and their expansion is severely impaired in MS patients [39]. Interestingly, human Treg cells constitutively express PRLR and their suppressive capacity is significantly abated when they are treated in vitro with PRL [40]. The activity of PRL on B and plasma cells has been extensively investigated in systemic lupus erithematosus (SLE), an autoimmune disorder characterized by deregulated humoral immune responses [41].…”

“…PRL might promote CNS repair by influencing oligodendrocyte progenitor cells (OPC) generation and oligodendrocyte proliferation [29], and favoring remyelination [29], neuroprotection [25,26,27,28] and neurogenesis [21,22,23,24]. However, PRL might also promote CNS damage by breaking B cell tolerance [42,43,44,45,46], sustaining autoantibody (autoAb) production [45] and macrophage release of cytokines [30,31,32] and stimulating autoreactive T cells [37,40]. …”

Prolactin Levels Correlate with Abnormal B Cell Maturation in MRL and MRL/lpr Mouse Models of Systemic Lupus Erythematosus-Like Disease

“…Different isoforms of the PRL receptor have been found to be generated by alternative splicing at the 3′ end and variation in the intracellular domain length [3, 5, 6]. The PRL receptor is expressed in many immune cell types, mainly B cells, and also T cells, monocytes, macrophages, natural killer (NK) cells, and thymic epithelial cells [7, 8], and its activation induces transcriptional programs involved in various cellular functions such as proliferation, differentiation, and cytokine production. Hence, PRL has been implicated as a modulator of both cellular and humoural immunity [8–11].…”