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Thymic stromal lymphopoietin is expressed in the intact central nervous system and upregulated in the myelin-degenerative central nervous system.

Kitic M, Wimmer I, Adzemovic M, Kögl N, Rudel A, Lassmann H, Bradl M - Glia (2014)

Bottom Line: Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine expressed at barrier surfaces of the skin, gut, nose, lung, and the maternal/fetal interphase.At these sites, it is important for the generation and maintenance of non-inflammatory, tissue-resident dendritic cell responses.We show here that TSLP is also expressed in the central nervous system (CNS) where it is produced by choroid plexus epithelial cells and astrocytes in the spinal cord.

View Article: PubMed Central - PubMed

Affiliation: Medical University Vienna, Center for Brain Research, Department of Neuroimmunology, Spitalgasse 4, 1090, Vienna, Austria.

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The expression of TSLP receptor chains in microglia and in MHC class II+ cells of the meningeal DC network. (a, b) FACSorted microglia of 6 wildtype (MG_wt) and 6 PLP-transgenic (MG_tg) 10–12 months old Lewis rats, FACSorted MHC class II+ cells of the meningeal DC network isolated from 13 wildtype 5 to 6 month old Lewis rats, and purified rat brain endothelial cells (EC) were tested by qPCR for the expression of both chains of a functional TSLP receptor, that is, for TSLPR (a) and IL-7Rα (b) in relation to the house keeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The expression of Tslpr was further corroborated by end-point polymerase chain reactions, and the expression of the IL-7Rα by gene expression studies (data not shown). Microglia in the spinal cord gray matter of PLP-transgenic rats was stained with ED1 (c) to reveal the presence of CD68, and with OX-6 (d) to reveal the presence of MHC class II products. In both cases, positive reaction products are brown, and the nuclei counterstained with hematoxylin are blue. (e) Flow cytometric analysis of microglia isolated from the wt or PLP-transgenic CNS, using IgG1 as an isotype control, and antibodies against CD80 and CD86. Note the upregulation of CD86 on microglia derived from PLP-transgenic rats.
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fig03: The expression of TSLP receptor chains in microglia and in MHC class II+ cells of the meningeal DC network. (a, b) FACSorted microglia of 6 wildtype (MG_wt) and 6 PLP-transgenic (MG_tg) 10–12 months old Lewis rats, FACSorted MHC class II+ cells of the meningeal DC network isolated from 13 wildtype 5 to 6 month old Lewis rats, and purified rat brain endothelial cells (EC) were tested by qPCR for the expression of both chains of a functional TSLP receptor, that is, for TSLPR (a) and IL-7Rα (b) in relation to the house keeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The expression of Tslpr was further corroborated by end-point polymerase chain reactions, and the expression of the IL-7Rα by gene expression studies (data not shown). Microglia in the spinal cord gray matter of PLP-transgenic rats was stained with ED1 (c) to reveal the presence of CD68, and with OX-6 (d) to reveal the presence of MHC class II products. In both cases, positive reaction products are brown, and the nuclei counterstained with hematoxylin are blue. (e) Flow cytometric analysis of microglia isolated from the wt or PLP-transgenic CNS, using IgG1 as an isotype control, and antibodies against CD80 and CD86. Note the upregulation of CD86 on microglia derived from PLP-transgenic rats.

Mentions: It has been described that TSLP preferentially stimulates myeloid cells (Qiao et al., 2011; Reche et al., 2001), and that DCs and monocytes coexpress TSLPR and IL-7Rα (Reche et al., 2001). Since microglia and monocytes share the ability to differentiate along the macrophage and DC lineage under several different pathological conditions (Fischer and Reichmann, 2001; Reichmann et al., 2002; Santambrogio et al., 2001), we analyzed by qPCR whether DCs from the meningeal DC network or microglial cells from the spinal cord contain the molecular machinery needed for TSLP recognition, that is, a functional TSLP receptor dimer consisting of the TSLP-specific receptor chain (TSLPR) and the common IL-7 receptor alpha chain (IL-7Rα). We found that the meningeal MHC class II+ DCs and spinal cord microglia produced transcripts encoding both the IL-7Rα chain and the TSLPR and were hence able to form a functional receptor for TSLP recognition (Fig. 3).


Thymic stromal lymphopoietin is expressed in the intact central nervous system and upregulated in the myelin-degenerative central nervous system.

Kitic M, Wimmer I, Adzemovic M, Kögl N, Rudel A, Lassmann H, Bradl M - Glia (2014)

The expression of TSLP receptor chains in microglia and in MHC class II+ cells of the meningeal DC network. (a, b) FACSorted microglia of 6 wildtype (MG_wt) and 6 PLP-transgenic (MG_tg) 10–12 months old Lewis rats, FACSorted MHC class II+ cells of the meningeal DC network isolated from 13 wildtype 5 to 6 month old Lewis rats, and purified rat brain endothelial cells (EC) were tested by qPCR for the expression of both chains of a functional TSLP receptor, that is, for TSLPR (a) and IL-7Rα (b) in relation to the house keeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The expression of Tslpr was further corroborated by end-point polymerase chain reactions, and the expression of the IL-7Rα by gene expression studies (data not shown). Microglia in the spinal cord gray matter of PLP-transgenic rats was stained with ED1 (c) to reveal the presence of CD68, and with OX-6 (d) to reveal the presence of MHC class II products. In both cases, positive reaction products are brown, and the nuclei counterstained with hematoxylin are blue. (e) Flow cytometric analysis of microglia isolated from the wt or PLP-transgenic CNS, using IgG1 as an isotype control, and antibodies against CD80 and CD86. Note the upregulation of CD86 on microglia derived from PLP-transgenic rats.
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Related In: Results  -  Collection

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fig03: The expression of TSLP receptor chains in microglia and in MHC class II+ cells of the meningeal DC network. (a, b) FACSorted microglia of 6 wildtype (MG_wt) and 6 PLP-transgenic (MG_tg) 10–12 months old Lewis rats, FACSorted MHC class II+ cells of the meningeal DC network isolated from 13 wildtype 5 to 6 month old Lewis rats, and purified rat brain endothelial cells (EC) were tested by qPCR for the expression of both chains of a functional TSLP receptor, that is, for TSLPR (a) and IL-7Rα (b) in relation to the house keeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The expression of Tslpr was further corroborated by end-point polymerase chain reactions, and the expression of the IL-7Rα by gene expression studies (data not shown). Microglia in the spinal cord gray matter of PLP-transgenic rats was stained with ED1 (c) to reveal the presence of CD68, and with OX-6 (d) to reveal the presence of MHC class II products. In both cases, positive reaction products are brown, and the nuclei counterstained with hematoxylin are blue. (e) Flow cytometric analysis of microglia isolated from the wt or PLP-transgenic CNS, using IgG1 as an isotype control, and antibodies against CD80 and CD86. Note the upregulation of CD86 on microglia derived from PLP-transgenic rats.
Mentions: It has been described that TSLP preferentially stimulates myeloid cells (Qiao et al., 2011; Reche et al., 2001), and that DCs and monocytes coexpress TSLPR and IL-7Rα (Reche et al., 2001). Since microglia and monocytes share the ability to differentiate along the macrophage and DC lineage under several different pathological conditions (Fischer and Reichmann, 2001; Reichmann et al., 2002; Santambrogio et al., 2001), we analyzed by qPCR whether DCs from the meningeal DC network or microglial cells from the spinal cord contain the molecular machinery needed for TSLP recognition, that is, a functional TSLP receptor dimer consisting of the TSLP-specific receptor chain (TSLPR) and the common IL-7 receptor alpha chain (IL-7Rα). We found that the meningeal MHC class II+ DCs and spinal cord microglia produced transcripts encoding both the IL-7Rα chain and the TSLPR and were hence able to form a functional receptor for TSLP recognition (Fig. 3).

Bottom Line: Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine expressed at barrier surfaces of the skin, gut, nose, lung, and the maternal/fetal interphase.At these sites, it is important for the generation and maintenance of non-inflammatory, tissue-resident dendritic cell responses.We show here that TSLP is also expressed in the central nervous system (CNS) where it is produced by choroid plexus epithelial cells and astrocytes in the spinal cord.

View Article: PubMed Central - PubMed

Affiliation: Medical University Vienna, Center for Brain Research, Department of Neuroimmunology, Spitalgasse 4, 1090, Vienna, Austria.

Show MeSH
Related in: MedlinePlus