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

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

doi:10.1111/exd.12914

Stephen E P Smith, Adam G Schrum + Show 4 more

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https://doi.org/10.1111/exd.12914

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Journal: Experimental dermatology	Publication Date: Feb 10, 2016
Citations: 3	License type: CC BY 4.0

Affiliation: Mayo Clinic, Jackson Laboratory

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.

Highlights

Alopecia areata (AA) is among the most common autoimmune disorders, with a lifetime incidence recently reported at 2.1% [1]
Timed-pregnant female wild-type B6 mice were electroporated in the tibialis anterior muscle with the mammalian expression vector pCAGGS encoding mouse IL-6 or LacZ on embryonic day (E) 12.5, as previously described [17]
A model of maternal immune activation was used in which pregnant B6 females were electroporated intramuscularly with an expression vector for temporary transgenic expression of IL-6

Summary

Introduction

Alopecia areata (AA) is among the most common autoimmune disorders, with a lifetime incidence recently reported at 2.1% [1]. Adoptive transfer experiments and human skin transplanted onto immunodeficient mice suggest that the disease is autoimmune mediated and that T cells play a significant role [3]. IL-6 is a critical causal factor in the maternal immune activation model of schizophrenia and autism, where inflammatory cytokine production in pregnant mice leads to permanent changes in utero to brain and immune systems in offspring [10,11]. Taken together, these observations suggested that IL-6-mediated maternal immune activation might interfere with normal hair development of progeny via an immune-mediated mechanism

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