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Interferon-gamma-deficient mice are resistant to the development of alopecia areata.
Br J Dermatol. 2006 Sep; 155(3):515-21.BJ

Abstract

BACKGROUND

Alopecia areata (AA) is a T-cell mediated putative autoimmune disease of hair follicles, which can be transferred by CD4(+) T cells. However, whether T-helper (Th) 1 or Th2 cytokines are predominant has not yet been defined.

OBJECTIVES

To elucidate the importance of Th1 cells in the pathogenesis of AA we investigated the functional role of interferon (IFN)-gamma in the experimental induction of AA.

METHODS

AA was experimentally induced by grafting full-thickness skin from AA-affected C3H/HeJ mice on to C3H/HeJ mice with a targeted deletion of the Th1 cytokine IFN-gamma gene (IFNgamma(-/-)) and on to wild-type mice (IFNgamma(+/+)).

RESULTS

While 90% of wild-type mice developed AA, none of the IFNgamma(-/-) mice exhibited hair loss. Immunohistochemistry of skin sections revealed a dense perifollicular and intrafollicular infiltrate of CD4(+) and CD8(+) T cells in controls, while in IFNgamma(-/-) mice skin-infiltrating CD8(+) T cells were absent and the number of CD4(+) cells was significantly reduced. Aberrant expression of major histocompatibility complex class I and II molecules in the putative immune-privileged infrainfundibular site of the hair follicle was found to be weaker in AA-resistant IFNgamma(-/-) mice than in control mice with AA. Flow cytometry revealed that leucocytes of IFNgamma(-/-) mice did not respond to the transfer of AA-affected skin. As distinct from IFNgamma(+/+) mice, neither T-cell activation markers nor Th1 cytokines were upregulated in draining lymph node cells or skin-infiltrating leucocytes of AA-resistant IFNgamma(-/-) mice. However, there was no evidence for a shift towards a Th2 cytokine profile, nor for upregulation of regulatory T cells in IFNgamma(-/-) mice.

CONCLUSIONS

IFNgamma(-/-) mice fail to activate Th1 cells in response to the transplanted (auto)antigens, which suggests an essential requirement for IFN-gamma-mediated Th1 activation in the induction of AA.

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Authors+Show Affiliations

Freyschmidt-Paul P
Department of Dermatology, Philipp University, Deutschhausstrasse 9, 35033 Marburg, Germany. freyschm@med.uni-marburg.de
McElwee KJ
No affiliation info available
Hoffmann R
No affiliation info available
Sundberg JP
No affiliation info available
Vitacolonna M
No affiliation info available
Kissling S
No affiliation info available
Zöller M
No affiliation info available

MeSH

Alopecia AreataAnimalsAutoimmune DiseasesCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesFemaleHair FollicleHistocompatibility Antigens Class IHistocompatibility Antigens Class IIInterferon-gammaLymph NodesLymphocyte ActivationMaleMiceMice, Inbred C3HMice, KnockoutSkinSkin TransplantationTh1 CellsUp-Regulation

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16911275

Citation

Freyschmidt-Paul, P, et al. "Interferon-gamma-deficient Mice Are Resistant to the Development of Alopecia Areata." The British Journal of Dermatology, vol. 155, no. 3, 2006, pp. 515-21.
Freyschmidt-Paul P, McElwee KJ, Hoffmann R, et al. Interferon-gamma-deficient mice are resistant to the development of alopecia areata. Br J Dermatol. 2006;155(3):515-21.
Freyschmidt-Paul, P., McElwee, K. J., Hoffmann, R., Sundberg, J. P., Vitacolonna, M., Kissling, S., & Zöller, M. (2006). Interferon-gamma-deficient mice are resistant to the development of alopecia areata. The British Journal of Dermatology, 155(3), 515-21.
Freyschmidt-Paul P, et al. Interferon-gamma-deficient Mice Are Resistant to the Development of Alopecia Areata. Br J Dermatol. 2006;155(3):515-21. PubMed PMID: 16911275.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interferon-gamma-deficient mice are resistant to the development of alopecia areata. AU - Freyschmidt-Paul,P, AU - McElwee,K J, AU - Hoffmann,R, AU - Sundberg,J P, AU - Vitacolonna,M, AU - Kissling,S, AU - Zöller,M, PY - 2006/8/17/pubmed PY - 2007/1/12/medline PY - 2006/8/17/entrez SP - 515 EP - 21 JF - The British journal of dermatology JO - Br J Dermatol VL - 155 IS - 3 N2 - BACKGROUND: Alopecia areata (AA) is a T-cell mediated putative autoimmune disease of hair follicles, which can be transferred by CD4(+) T cells. However, whether T-helper (Th) 1 or Th2 cytokines are predominant has not yet been defined. OBJECTIVES: To elucidate the importance of Th1 cells in the pathogenesis of AA we investigated the functional role of interferon (IFN)-gamma in the experimental induction of AA. METHODS: AA was experimentally induced by grafting full-thickness skin from AA-affected C3H/HeJ mice on to C3H/HeJ mice with a targeted deletion of the Th1 cytokine IFN-gamma gene (IFNgamma(-/-)) and on to wild-type mice (IFNgamma(+/+)). RESULTS: While 90% of wild-type mice developed AA, none of the IFNgamma(-/-) mice exhibited hair loss. Immunohistochemistry of skin sections revealed a dense perifollicular and intrafollicular infiltrate of CD4(+) and CD8(+) T cells in controls, while in IFNgamma(-/-) mice skin-infiltrating CD8(+) T cells were absent and the number of CD4(+) cells was significantly reduced. Aberrant expression of major histocompatibility complex class I and II molecules in the putative immune-privileged infrainfundibular site of the hair follicle was found to be weaker in AA-resistant IFNgamma(-/-) mice than in control mice with AA. Flow cytometry revealed that leucocytes of IFNgamma(-/-) mice did not respond to the transfer of AA-affected skin. As distinct from IFNgamma(+/+) mice, neither T-cell activation markers nor Th1 cytokines were upregulated in draining lymph node cells or skin-infiltrating leucocytes of AA-resistant IFNgamma(-/-) mice. However, there was no evidence for a shift towards a Th2 cytokine profile, nor for upregulation of regulatory T cells in IFNgamma(-/-) mice. CONCLUSIONS: IFNgamma(-/-) mice fail to activate Th1 cells in response to the transplanted (auto)antigens, which suggests an essential requirement for IFN-gamma-mediated Th1 activation in the induction of AA. SN - 0007-0963 UR - https://www.unboundmedicine.com/medline/citation/16911275/Interferon_gamma_deficient_mice_are_resistant_to_the_development_of_alopecia_areata_ L2 - https://doi.org/10.1111/j.1365-2133.2006.07377.x DB - PRIME DP - Unbound Medicine ER -