Maternal IL-6 can cause T-cell-mediated juvenile alopecia by non-scarring follicular dystrophy in mice

Stephen E.P. Smith, Rachel L.G. Maus, Tessa R. Davis, John P. Sundberg, Diana Gil, Adam G. Schrum

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Aiming to decipher immunological mechanisms of the autoimmune disorder alopecia areata (AA), we hypothesized that interleukin-6 (IL-6) might be associated with juvenile-onset AA, for which there is currently no experimental model. Upon intramuscular transgenesis to overexpress IL-6 in pregnant female C57BL/6 (B6) mice, we found that the offspring displayed an initial normal and complete juvenile hair growth cycle, but developed alopecia around postnatal day 18. This alopecia was patchy and reversible (non-scarring) and was associated with upregulation of Ulbp1 expression, the only mouse homolog of the human AA-associated ULBP3 gene. Alopecia was also associated with inflammatory infiltration of hair follicles by lymphocytes, including alpha-beta T cells, which contributed to surface hair loss. Despite these apparently shared traits with AA, lesions were dominated by follicular dystrophy that was atypical of human AA disease, sharing some traits consistent with B6 alopecia and dermatitis. Additionally, juvenile-onset alopecia was followed by complete, spontaneous recovery of surface hair, without recurrence of hair loss. Prolonging exposure to IL-6 prolonged the time to recovery, but once recovered, repeating high-dose IL-6 exposure de novo did not re-induce alopecia. These data suggest that although substantial molecular and cellular pathways may be shared, functionally similar alopecia disorders can occur via distinct pathological mechanisms.

Original languageEnglish (US)
Pages (from-to)223-228
Number of pages6
JournalExperimental Dermatology
Volume25
Issue number3
DOIs
StatePublished - Mar 1 2016

Keywords

  • Alopecia areata
  • B6 alopecia and dermatitis
  • Interleukin-6
  • Juvenile onset
  • Lymphocyte
  • Maternal immune activation
  • T cell

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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    Smith, S. E. P., Maus, R. L. G., Davis, T. R., Sundberg, J. P., Gil, D., & Schrum, A. G. (2016). Maternal IL-6 can cause T-cell-mediated juvenile alopecia by non-scarring follicular dystrophy in mice. Experimental Dermatology, 25(3), 223-228. https://doi.org/10.1111/exd.12914