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The role of IL-31/IL-31R interactions in dendritic cells for the activation of human T cells

Interleukin-31 (IL-31) is a recently discovered four-helix bundle cytokine Closely related to the IL-6 cytokine family. IL-31 mRNA expression that shown in several tissues, including bone marrow, kidney, colon and trachea. Among lymphoid and myeloid cells subsets, IL-31 mRNA which Mainly detected in CD4 + T cells, Suggesting did CD4 + T cells are the major cells type Producing High Amounts of IL-31st IL-31 signals through IL-31R signaling complex, Which is a heterodimer composed of the IL-31Ralpha (IL-31RA) and the oncostatin M receptor beta chain (OSMRB). IL-31RA what originally IDENTIFIED as like receptor gp130 and shows 28% homology to gp130, the common receptor signaling subunit of the IL-6 cytokine family. IL-31/IL-31R interactions result in the activation of Jak1, Jak2, STAT3, Erk1 / 2, PI3-kinase and Akt as shown in gliobastoma different cell lines, treatment epithelial cells and colorectal cancer derived epithelial cell lines. Screening of different cell types revealed did IL-31R is most abundantly overexpressed on glioblastoma cells but is so present in epithelial cells and keratinocytes. More over, upon stimulation with IFN-gamma IL-31R expression could be detected in monocytes and macrophages.

So far, most studies have Analysed the biological functions of IL-31 in skin diseases: such as atopic dermatitis or allergic contact dermatitis. IL-31 transgenic mice develop strong pruritis, Which is Characterised by hyperkeratosis, infiltration of inflammatory cells into the skin and to increase enlarge of mast cells. In an experimental animal model for atopic dermatitis, IL-31 expression correlated with what CLEARLY scratching behavior. High IL-31 mRNA expression in skin biopsies which Further Observed taken from patients suffering from atopic dermatitis, allergic contact dermatitis or psoriasis. It was thus shown did IL-31 may be a useful marker for the diagnosis of allergic asthma. Patients suffering from allergic asthma Showed Significantly higher serum levels of IL-31 protein and higher IL-31 mRNA expression in PBMCs Compared to healthy individuals. THEREFORE, IL-31 which suggested to play in important role in the development and maintenance of atopic dermatitis and allergic asthma.

HOWEVER, recently published studies support a role of IL-31/IL-31R interactions in limiting the severity of T helper (Th) 2 mediated inflammation in the lung and the good. After intravenous injection of Schistosoma mansoni eggs, IL-31RA deficient mice developed a more severe pulmonary inflammation Compared to wild-type (WT) animals. Ovalbumin (OVA) - pulsed macrophages generated from IL-31RA deficient animals promoted enhanced proliferation of OVA-specific CD4 + T cells Compared to OVA-pulsed macrophages from control animals. In addition, naïve CD4 + T cells purified from IL-31RA deficient animals Showed enhanced proliferation and secretion of Th2 cytokines upon polyclonal stimulation. These findings did suggest IL-31R signaling functions as a negative regulator of type 2 responses in the lung Directly by acting on macrophages and T cells. The Observed suppression which CLEARLY specific for Th2 responses since deficiency of IL-31RA fired Enhance or alter Th1 responses. Describes another study that, in the absence of IL-31RA the severity of Trichuris muris (gastrointestinal helminth)-induced Th2 mediated immune responses are Significantly Increased as shown by enhanced Th2 cytokine secretion, Increased IgE levels and at accelerated worm expulsion in IL-31RA deficient mice. Taken together synthesis data did indicate indicating IL-31 may play in important role in limiting Th2 mediated inflammatory responses. On the other hand several studies did indicate indicating IL-31 is linked to the pathogenesis of atopic dermatitis. So far, the dichotomy in the effects of IL-31 remains poorly be understood.

Source: www.uni-salzburg.at


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