Disease relevance of Tslp

• This indicates that TSLP contributes to lymphoid development and accounts for some of the residual lymphoid development in gamma(c) KO mice and presumably in patients with X-linked severe combined immunodeficiency [1].
• Here we report that TSLP overexpression in mice results in the development of mixed cryoglobulins, with renal involvement closely resembling cryoglobulinemic glomerulonephritis as it occurs in humans [2].
• TSLP transgenic animals developed polyclonal mixed cryoglobulinemia (type III) and a systemic inflammatory disease involving the kidney, spleen, liver, lung, and ears [2].
• Spontaneous atopic dermatitis in mice expressing an inducible thymic stromal lymphopoietin transgene specifically in the skin [3].
• FcgammaRIIb-/- mice had no significant renal pathology, whereas overexpression of TSLP induced a membranoproliferative glomerulonephritis, as previously established [4].

High impact information on Tslp

• These Lin(-)CD45R(lo-neg)CD19(+) cells responded to thymic stromal lymphopoietin and 'preferentially' reconstituted functional sIgM(hi)CD11b(+)CD5(lo-neg) B-1 B cells, but not sIgM(+)CD11b(-) B-2 B cells, in vivo [5].
• Lung-specific expression of a Tslp transgene induced airway inflammation and hyperreactivity characterized by T helper type 2 cytokines and increased immunoglobulin E [6].
• In addition, TSLP exerts an effect indirectly through DCs to promote Th2 differentiation of CD4+ T cells [7].
• Thymic stromal lymphopoietin (TSLP) is a cytokine that promotes CD4+ T cell homeostasis [7].
• The cytokine thymic stromal lymphopoietin (TSLP) has recently been implicated in the pathogenesis of atopic dermatitis (AD) and other allergic diseases in humans [3].

Chemical compound and disease context of Tslp

• Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis [8].
• Retinoid X receptor ablation in adult mouse keratinocytes generates an atopic dermatitis triggered by thymic stromal lymphopoietin [9].

Biological context of Tslp

• The gene encoding TSLP was mapped to murine chromosome 18 [10].
• The cellular receptor for murine thymic stromal lymphopoietin (TSLP) was detected in a variety of murine, but not human myelomonocytic cell lines by radioligand binding. cDNA clones encoding the receptor were isolated from a murine T helper cell cDNA library [11].
• B-cell development, including the IgM+ compartment, was unaffected by loss of the TSLP pathway, as were T lymphopoiesis and lymphocyte proliferation in vitro [12].
• TSLP induced phosphorylation of signal transducer and activator of transcription (STAT)-5 [13].
• Finally, we demonstrate that thymic stromal lymphopoietin, whose expression is rapidly and strongly induced in RXRalphabeta-ablated keratinocytes, plays a key role in initiating the skin and systemic AD-like pathologies [9].

Anatomical context of Tslp

• We studied the biological activities of TSLP in B cell development at distinct ages in the mouse [14].
• Pre-B cell receptor expression is necessary for thymic stromal lymphopoietin responsiveness in the bone marrow but not in the liver environment [14].
• A role for thymic stromal lymphopoietin in CD4(+) T cell development [1].
• In summary, we describe the cloning of human TSLP and its proliferative effects on a myeloid cell line [13].
• Inducible expression of the proallergic cytokine thymic stromal lymphopoietin in airway epithelial cells is controlled by NFkappaB [15].

Associations of Tslp with chemical compounds

• IL-7 has been studied extensively, but only recently has it become possible to unravel the role of TSLP in detail [14].
• Furthermore, topical application of retinoic acid receptor RARgamma-selective agonist BMS961 also induces TSLP expression either on its own or synergistically with 1alpha,25-(OH)(2)D(3) [8].

Other interactions of Tslp

• Additionally, CD4(+) T cells from TSLPR KO mice expanded less efficiently than WT CD4(+) T cells in irradiated hosts, and TSLP preferentially expanded CD4(+) T cells both in vitro and in vivo [1].
• We assessed the role of FcgammaRIIb in a mouse model of cryoglobulin-associated membranoproliferative glomerulonephritis induced by overexpression of thymic stromal lymphopoietin (TSLP) [4].
• IL-7 activity is complemented by two cytokines whose receptors share components of the IL-7 receptor: thymic stromal lymphopoietin (TSLP) and IL-15 [16].

Analytical, diagnostic and therapeutic context of Tslp

• TSLP had comitogenic activity for fetal thymocytes, but was not as potent as interleukin 7 in lobe submersion cultures [10].

References