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Thymic stromal lymphopoietin induces tight junction protein claudin-7 via NF-κB in dendritic cells

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Abstract

Epithelial-derived thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine that triggers dendritic cell (DC)-mediated Th2-type inflammatory responses. The activated DCs can penetrate the epithelium to directly take up antigen without compromising the barrier function. Although it is reported that DCs express tight junction molecules and can establish tight junction-like structures with adjacent epithelial cells to preserve the epithelial barrier, the regulation of expression of tight junction molecules in DCs remains unknown. In the present study, to investigate the mechanical regulation of expression of tight junction molecules in DCs, XS52 DCs that was a long-term DC line established from the epidermis of a newborn BALB/c mouse, were treated with TSLP or toll-like receptor (TLR) ligands. In XS52 cells, tight junction molecules claudin-1, -3, -4, -6, -7, -8, and occludin were detected. mRNA expression of TSLP receptor and all these tight junction molecules was significantly increased in activated XS52 cells after treatment with TSLP. In addition, expression of claudin-7 protein was increased in dose- and time-dependent manner. In XS52 cells, which express TLR2, TLR3, TLR4, and TLR7, but not TLR9, expression of claudin-7 protein was also increased after treatment with ligands of TLR2, TLR4 or TLR7/8, Pam3Cys-Ser-(Lys)4, LPS, or CL097. The NF-κB inhibitor IMD-0354 prevented upregulation of claudin-7 after treatment with TSLP or TLR ligands. These findings indicate that TSLP induces expression of tight junction protein claudin-7 in DCs via NF-κB as well as via TLRs and may control tight junctions of DCs to preserve the epithelial barrier during allergic inflammation.

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Abbreviations

TSLP:

Thymic stromal lymphopoietin

DC:

Dendritic cell

TLR:

Toll-like receptor

TIR:

Toll and interleukin-1 receptor

MyD88:

Myeloid differentiation primary response protein 88

JAM:

Junctional adhesion molecule

CAR:

Coxsackievirus-adenovirus receptor

ZO:

Zonula occludens

IL-7Rα:

IL-7 receptor α chain

TSLPR:

TSLP receptor chain

LC:

Langerhans cell

P3CSK4 :

Pam3Cys-Ser-(Lys)4

Poly (I:C):

Polyinosine-polycytidylic acid

rRNA:

Ribosomal RNA

DAPI:

4′, 6-diamidino-2-phenylindole dihydrochloride

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Acknowledgments

This work was supported by Grants-in-Aid from the National Project “Knowledge Cluster Initiative” (2nd stage, “Sapporo Biocluster Bio-S”), the Ministry of Education, Culture, Sports Science, and Technology, and the Ministry of Health, Labour and Welfare of Japan, the Akiyama Foundation, and the Japan Science and Technology Agency.

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Authors and Affiliations

  1. Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan

    Ryuta Kamekura, Jun-ichi Koizumi, Noriko Ogasawara, Mitsuru Go, Ken-ichi Takano & Tetsuo Himi

  2. Department of Pathology, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-ku, Sapporo, 060-8556, Japan

    Ryuta Kamekura, Takashi Kojima, Noriko Ogasawara, Masaki Murata, Satoshi Tanaka, Shingo Ichimiya & Norimasa Sawada

  3. Department of Medical Microbiology and Immunology, University of Toledo, Toledo, OH, USA

    Akira Takashima

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  1. Ryuta Kamekura
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  2. Takashi Kojima
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  3. Akira Takashima
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  4. Jun-ichi Koizumi
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  5. Noriko Ogasawara
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  12. Norimasa Sawada
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Correspondence to Takashi Kojima.

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Kamekura, R., Kojima, T., Takashima, A. et al. Thymic stromal lymphopoietin induces tight junction protein claudin-7 via NF-κB in dendritic cells. Histochem Cell Biol 133, 339–348 (2010). https://doi.org/10.1007/s00418-009-0674-1

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