Gene Expression Profiles of Peripheral and Cord Blood Mononuclear Cells Altered by Thymic Stromal Lymphopoietin

Abstract

Thymic stromal lymphopoietin (TSLP) was reported to induce dendritic cells to produce Th2-attracting chemokines, followed by allergic inflammation through stimulating not only CD4-positive T cells but also CD8-positive T cells. Therefore, in this experiment, GeneChip and hierarchical clustering were applied to screen the molecules in whole immunity triggered by TSLP directly and indirectly using both adult peripheral and cord blood mononuclear cells as well as isolated monocytes. Gene expression profiles screened a variety of molecules that are triggered by TSLP with or without CD40 ligation. In the profile, RNA expressions of indoleamine 2,3-dioxygenase, that is known to induce anergy of T cells and natural killer cells in protecting fetal rejection; many kinds of proteasomes that were reported to trigger cytokine production by inhibiting suppressors of NF-B; and several kinds of chemokines increased, whereas RNA expression of superoxide dismutase 1 decreased, which was unexpected but considered worthy of notice. Expression of chemokines at protein levels and enzymatic activity of indoleamine 2,3-dioxygenase was further confirmed to increase in the presence of TSLP using ELISA and HPLC, respectively. These results suggest that the advent of microarray technology may enable us to screen novel molecular targets to treat TSLP-related allergic inflammation. (Pediatr Res 57: 563-569, 2005) Abbreviations CBMC, cord blood mononuclear cell DC, dendritic cell IDO, indoleamine 2,3-dioxygenase IFN-␥, interferon-␥ MCP1, monocyte chemotactic protein-1 M-CSF, macrophage-colony stimulating factor MDC, macrophage-derived chemokine PBMC, peripheral blood mononuclear cell TARC, thymus and activation-regulated chemokine Th1, T helper 1 Th2, T helper 2 TNF-␣, tumor necrosis factor-␣ TSLP, thymic stromal lymphopoietin Aberrant skewing to either T helper type 1 (Th1) or T helper type 2 (Th2) cells may cause autoimmune or allergic inflammatory disorders. The allergic diseases, including atopic eczema, food allergy, bronchial asthma, and allergic rhinoconjunctivitis, are considered the clinical results of inflammation triggered by dysregulated production of Th2-derived cytokines (1). Indeed, development of allergic inflammation in mice was prevented by administration of certain mycobacterial strains through a shift from Th2 to Th1 immune responses (2). In addition to allergic inflammatory disorders, cord and neonatal blood are known to demonstrate Th2 dominant immunity (3), which is not a pathologic but rather a physiologic condition and explains the reduced reactivity of the maternal immune system against the fetal allograft (4). Despite Th2 skewing, neonates rarely have allergic reactions, and there is a low frequency of graft-versus-host disease in cord blood transplantation (5). Thus, cord blood may have different immunologic characteristics from adult blood, although these differences are not fully delineated.Thymic stromal lymphopoietin (TSLP) has been cloned initially as a novel cytokine to promote B cell development in mice (6...

Thymic Stromal Lymphopoietin Is Up‐Regulated in the Skin of Patients With Systemic Sclerosis and Induces Profibrotic Genes and Intracellular Signaling That Overlap With Those Induced by Interleukin‐13 and Transforming Growth Factor β

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