Thymic stromal lymphopoietin (TSLP) signaling (Homo sapiens)

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Thymic stromal lymphopoietin (TSLP) is a type I cytokine member of interleukin-2 cytokine family. TSLP signals through interleukin-7 receptor a chain (IL-7Ra) and the TSLP receptor subunit (TSLPR), heterodimeric receptor complex. TSLP is expressed by epithelial cells of the lung, skin, gut, Hassall's corpuscles (HCs) in thymic medulla, mucosa-associated lymphoid tissues and tonsils. Apart from epithelial cells, TSLP is also expressed by primary skin keratinocytes, smooth muscle cells and lung fibroblasts. It has also been shown that heart, liver, spleen and prostate have higher expression levels of TSLP compared to lung, skeletal muscle, kidney, spleen, ovary, small intestine and colon.

TSLP can activate CD4+ T cells and CD8+ T cells in mice and induces B-cell proliferation and differentiation in humans. It also enhances maturation and proliferation of dendritic cells and naive T-cells, respectively. It has also been shown to induce the release of T-cell attracting chemokines from monocytes. In combination with interleukin-1 and tumor necrosis factor, TSLP can stimulate the production of Th2 cytokines by human mast cells [10]. Further, TSLP is also involved in mediating many cell functions invasion of trophobalsts, chemotaxis and survival of eosinophils.

Binding to its receptor complex, TSLP can activate multiple signal transduction pathways. Previously, studies have shown that stimulation of IL7R/TSLPR complex by TSLP induces the phosphorylation and activation of Janus kinases (JAKs). Activated JAKs, in turn, regulates the activity of signal transducers and activators of transcription (STAT) factors which includes STAT1, STAT3, STAT4, STAT5A, STAT5B and STAT6. Several other proteins such as AKT1, ERK1/2, JNKs, ribosomal protein S6 kinase and 4E-BP1 have also shown to be activated upon TSLP stimulation. Recently, our group carried out SILAC-based quantitative phosphoproteomic analysis to identify molecules that are differentially phosphorylated upon stimulation with TSLP. Our results revealed TSLP regulated phosphorylation of 226 proteins including several members of the SRC and TEC family of kinases.

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