Role of TRPV3 in immune response to development of dermatitis - PubMed (original) (raw)

Role of TRPV3 in immune response to development of dermatitis

Kinichi Imura et al. J Inflamm (Lond). 2009.

Abstract

Background: Recently, it has been reported that the Gly573Ser substitution of transient receptor potential V3 (TRPV3) leads to increased ion-channel activity in keratinocytes. Our previous studies have indicated that the spontaneous hairless and dermatitis phenotypes of DS-Nh mice, which were newly established as an animal model of atopic dermatitis (AD), are caused by TRPV3Gly573Ser. Although this substitution causes hairlessness in several kinds of rodents, in our investigations, dermatitis developed in only a few animals. Here, we generated NC/Nga-Nh mice to elucidate the role of TRPV3Gly573Ser in NC/Nga mice, which is one of the most studied animal models of AD.

Methods: To establish and validate the new AD animal model, NC/Nga-Nh mice were generated using NC/Nga and DS-Nh mice, and their clinical features were compared. Next, T-cell receptor (TCR) Vbeta usage in splenocytes, evaluation of bacterial colonization, and serological and histological analyses were carried out. Finally, repeated-hapten-application dermatitis was induced in these mice.

Results: NC/Nga-Nh mice did not develop spontaneous dermatitis, whereas DS-Nh mice displayed this phenotype when maintained under the same conditions. Serological analysis indicated that there really was a phenotypic difference between these mice, and TCR repertoire analysis indicated that TCRVbeta haplotypes played an important role in the development of dermatitis. Artificial dermatitis developed in DS and NC/Nga-Nh mice, but not in DS-Nh and NC/Nga mice. Histological and serological analyses indicated that mouse strains were listed in descending order of number of skin mast cells: DS-Nh > DS approximately NC/Nga-Nh > NC/Nga, and serum IgE levels were increased after 2,4,6 trinitrochlorobenzene application in these mice. Serum IgE level in DS-Nh mice was lower than that mesured in other strains.

Conclusion: Our results confirm the contribution of the TRPV3Gly573Ser gene to the development of repeated hapten dermatitis, but not spontaneous dermatitis in NC/Nga mice.

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Figures

Figure 1

Figure 1

Disease symptoms in DS-Nh and NC/Nga-Nh mice. (A) Clinical features of DS-Nh and NC/Nga-Nh mice at 20 weeks of age kept under conventional or SPF conditions. (B) Evaluation of scratching and rubbing behavior in both strains at 20 weeks of age (n = 8) (SPF, kept under SPF conditions; Conv, kept under conventional conditions). White bar represents mean value of the grouped mice. (**, ##: significant differences at p < 0.01).

Figure 2

Figure 2

TCRBV repertoire analysis. The TCRBV repertoires in spleen cells from five DS-Nh or NC/Nga-Nh mice without in vitro stimulation.Bar indicates mean +2 SD of the TCRBV repertoires in spleen cells from five DS-Nh or NC/Nga-Nh mice without in vitro stimulation. Each dot indicates the percentage frequency of _TCRBV_-bearing T cells in spleen cells stimulated in vitro with SEC.

Figure 3

Figure 3

Bacterial colonization of skin lesions. (A) Isolation and identification of staphylococcal strains on the skin surface in both strains at 20 weeks of age (n = 5). (B) Measurement of serum levels of antibody to PGN in both strains at 20 weeks of age (n = 5).

Figure 4

Figure 4

Repeated application of TNCB in DS, DS-Nh, NC/Nga and NC/Nga-Nh mice. (A) Evaluation of dermatitis in these mice. Each value represents mean ± SD of four or five mice. (B and C) Clinical features of skin in these mice. (D) Clinical features of joints in DS-Nh mice. Arrows indicate arthritis-like lesions.

Figure 5

Figure 5

Number of mast cells in skin from DS-Nh, NC/Nga-Nh and control mice. Data represent the mean ± SD of six fields in six tissue samples. (**, ##: significant differences at p < 0.01), #: significant differences at p < 0.05).

Figure 6

Figure 6

Total serum IgE levels. Data are expressed as means ± SD of four or five mice. (*: significant differences at p < 0.05).

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