FcϵRI-mediated thymic stromal lymphopoietin production by interleukin-4-primed human mast cells

Abstract

A significant increase of mRNA expression of thymic stromal lymphopoietin (TSLP) has been reported in the bronchial mast cells (MCs) of asthmatic subjects; however, the mechanism underlying the upregulation of TSLP mRNA and protein remains unknown.FceRI-mediated activation of human MCs upregulated TSLP mRNA expression by 5.2¡2.9-fold, while activation of the MCs using lipopolysaccharide and polyriboinosinic:polyribocytidylic acid failed to upregulate TSLP. Stimulation of MCs with interleukin (IL)-4 alone did not affect the TSLP mRNA expression, while pre-incubation of MCs with IL-4 for 48 h significantly enhanced the FceRI-mediated TSLP mRNA expression (by 53.7¡15.9-fold; p,0.05) and the amount of TSLP in the cell pellets increased significantly from 23.4¡4.3 pg?mL -1 to 121.5¡3.7 pg?mL -1 (p,0.0001).However, the released TSLP was rapidly degraded by proteases that were released by MCs. We identified the population of cells expressing TSLP in the lungs of 16 asthmatic and 11 control subjects by immunohistochemistry. The percentage of TSLP-positive MCs in the total population of MCs was significantly increased in asthmatic airways (p,0.0001). Thus, MCs are able to store TSLP intracellularly and to produce TSLP following aggregation of FceRI in the presence of IL-4.

Regulation of type 2 immunity to helminths by mast cells

“…It has been reported that MCs are able to produce all three cytokines, [28][29][30] thus, one possibility is that MCs themselves contribute to the enhanced expression of these factors following Hp infection. However, it is unlikely that MCs-a relatively rare population in the steady-state/ early-infected intestine-produce sufficient quantities of these cytokines alone.…”

Thymic Stromal Lymphopoietin Contributes to Myeloid Hyperplasia and Increased Immunoglobulins, But Not Epidermal Hyperplasia, in RabGEF1-Deficient Mice

“…We do not know whether RabGEF1 has this effect through direct or indirect mechanisms, but it is known that epithelia of the skin, intestine, and respiratory tract are the major sources of TSLP 3 and that production of TSLP in these epithelial cells can be induced by active vitamin D 3 (1a,25-(OH) 2 D 3 ) or its low calcemic analog, 31 proinflammatory cytokines, [32][33][34][35] and various TLR ligands. 33,35 In addition, bone marrow-derived cells, including human mast cells 36 and mouse basophils, 37 also can produce TSLP. While current understanding of the mechanisms regulating TSLP production is rather limited, NF-B-binding sites are present in the promoters of both human and mouse TSLP genes, 35 and there is evidence supporting an involvement of NF-B pathways in the regulation of TSLP production.…”

The role of infection in the pathogenesis of allergodermatoses

“…В первый раз ТСЛП был об-наружен в культуре тимических клеток, откуда по-лучил свое название. Анализ библиотек кодирую-щих ДНК клеточных линий и первичных культур различных тканей показал, что не только кератино-циты и эпителиальные клетки, но и гладкие мышеч-ные клетки, легочные фибробласты, активирован-ные связыванием IgE тучные клетки, а также акти-вированные дендритные клетки в больших количе-ствах экспрессируют и продуцируют ТСЛП [18][19][20][21][22][23]. Продукция ТСЛП усиливается разными цитокина-ми: ИЛ-4, ИЛ-13, ИЛ-1b, ИЛ-25, ИЛ-33, фактором некроза опухоли альфа (ФНО-α), интерферонами-α и -β и другими [19,20,22].…”