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Epidermal filaggrin deficiency mediates increased systemic T‐helper 17 immune response
Author(s) -
Bonefeld C.M.,
Petersen T.H.,
Bandier J.,
Agerbeck C.,
Linneberg A.,
RossHansen K.,
Stender S.,
Szecsi P.B.,
Johansen J.D.,
Geisler C.,
Thyssen J.P.
Publication year - 2016
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.14570
Subject(s) - filaggrin , immune system , immunology , flow cytometry , cytokine , biology , microbiology and biotechnology , atopic dermatitis
Summary Background Cellular T‐helper (Th)17 infiltrates dominate skin inflammation in filaggrin‐deficient flaky tail ( ft/ft ) mice, and Th17 cells are found in both the skin and blood of patients with acute atopic dermatitis. However, the potential role of loss‐of‐function mutations in the filaggrin gene ( FLG ) for increased peripheral Th17 cells is unclear. Objectives To study whether mutations in FLG influence the frequency of peripheral Th17 cells. Methods We studied blood samples from six adults with mutations in FLG and five controls without mutations for frequencies of cytokine‐producing CD 4 + T cells. We evaluated ft/ft mice and wild‐type ( WT ) control mice for interleukin ( IL )‐17‐producing CD 4 + T cells in naive mice and following 2,4‐dinitrofluorobenzene ( DNFB ) challenge. In addition, the T‐cell receptor ( TCR ) Vβ‐chain repertoire was analysed by flow cytometry. Results Human studies showed increased frequency of peripheral Th17 cells in FLG mutation carriers when compared with WT individuals. Mouse studies showed increased frequency of peripheral Th17 cells in adult ft/ft mice but not in 2‐week‐old ft/ft mice. Moreover, altered TCR Vβ‐chain repertoire was found in ft/ft mice when compared with WT mice. An increased frequency of CD 4 + Vβ10 + T cells producing IL ‐17 was found in the spleen of adult ft/ft mice when compared with WT mice. Finally, DNFB challenge induced an increased number of Th17 cells in ft/ft mice compared with WT mice. Conclusions Deficiency of filaggrin appeared to be a driver of increased peripheral levels of Th17 cells. This increase must be acquired as peripheral Th17 cells were found in adult ft/ft mice but not in 2‐week‐old ft/ft mice indicating involvement of exogenous factors.