Alopecia Areata Induced in C3H/HeJ Mice by Interferon-Gamma: Evidence for Loss of Immune Privilege

Gilhar, Amos; Kam, Yossi; Assy, Bedia; Kalish, Richard S.

doi:10.1111/j.0022-202x.2004.23580.x

Cited by 84 publications

(73 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…C3H/HeJ female mice were injected intravenously with IFN-g to induce follicular MHC. These mice demonstrated an increased rate of development of AA (90). This is in line with both the immune privilege collapse hypothesis and the finding that IFN-g-deficient mice are resistant to AA (6).…”

Section: Ifn-g Insupporting

confidence: 81%

Lymphocytes, neuropeptides, and genes involved in alopecia areata

Gilhar¹,

Paus²,

Kalish³

2007

J. Clin. Invest.

Self Cite

272

278

View full text Add to dashboard Cite

Many lessons in autoimmunity -particularly relating to the role of immune privilege and the interplay between genetics and neuroimmunology -can be learned from the study of alopecia areata, the most common cause of inflammation-induced hair loss. Alopecia areata is now understood to represent an organ-restricted, T cell-mediated autoimmune disease of hair follicles. Disease induction is associated with collapse of hair follicle immune privilege in both humans and in animal models. Here, the role of HLA associations, other immunogenetic factors, and neuroendocrine parameters in alopecia areata pathogenesis are reviewed. This instructive and clinically significant model disease deserves more widespread interest in the immunology community.Nonstandard abbreviations used: AA, alopecia areata; AIRE, autoimmune regulator; APECED, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; IP-10, IFN-g-inducible protein 10; MIC, MHC class I chain-related; MIF, macrophage migration inhibitory factor; α-MSH, α-melanocyte-stimulating hormone; NALP1, NACHT leucine-rich-repeat protein 1; NGF, nerve growth factor.

show abstract

Section: Ifn-g Insupporting

confidence: 81%

Lymphocytes, neuropeptides, and genes involved in alopecia areata

Gilhar¹,

Paus²,

Kalish³

2007

J. Clin. Invest.

Self Cite

272

278

View full text Add to dashboard Cite

show abstract

“…In a previous study, when Ifng was injected into nonalopecic genetically susceptible C3H/HeJ mice, alopecia was induced with an ectopic expression of MHC class I and class II on follicular epithelium. 19 Our study demonstrated that anti-Ifng neutralizing antibody injections ameliorated alopecia in C3H/HeJ mice ( Figure 4). Taken together, Ifng plays a pivotal role both in the induction and the maintenance of alopecia in genetically susceptible C3H/HeJ mice.…”

Section: Discussionmentioning

confidence: 55%

Controlled Delivery of T-box21 Small Interfering RNA Ameliorates Autoimmune Alopecia (Alopecia Areata) in a C3H/HeJ Mouse Model

Nakamura

Tabata

et al. 2008

The American Journal of Pathology

View full text Add to dashboard Cite

Autoimmune alopecia (alopecia areata) is considered to be triggered by a collapse of immune privilege in hair follicles. Here we confirmed that infiltrating CD4 T lymphocytes around hair follicles of patients with alopecia areata were primarily CCR5-positive with few CCR4-positive cells, suggesting a dominant role of Th1 cells in the alopecic lesion. Given this finding, we sought to elucidate the effect of cytokine therapy in C3H/HeJ mice, a mouse model of alopecia areata, by applying recombinant interleukin-4 and neutralizing anti-interferon-␥ antibody. We found that local injections of both interleukin-4 and neutralizing anti-interferon-␥ antibody effectively treated alopecia in C3H/ HeJ mice. Results from immunohistochemistry and semiquantitative reverse transcription-polymerase chain reaction demonstrated that intralesional injection of interleukin-4 suppressed CD8 T cell infiltrates around the hair follicles and repressed enhanced interferon-␥ mRNA expression in the affected alopecic skin. Furthermore, Th1 transcription factor T-box21 small interfering RNAs conjugated to cationized gelatin showed mitigating effects on alopecia in C3H/HeJ mice, resulting in the restoration of hair shaft elongation. Taken together, the use of gelatin-small interfering RNA conjugates promises to be a novel, efficient, and safe tool as an alternative gene therapy for the treatment of various human diseases. To our knowledge, this is the first report of effective controlled delivery of small interfering RNA using biodegradable cationized gelatin microspheres in an animal model of disease.

show abstract

“…Furthermore, IFNγ can be used to induce AA in C3H/HeJ mice [68], though this observation has been difficult to replicate [69]. However, mice genetically deficient in IFNγ are resistant to the development of AA [70].…”

Section: Immune Privilege Collapse In Alopecia Areatamentioning

confidence: 99%

“…In small scale studies, anti-IFNγ treatment showed significant hair restoration potential in patients with AA [185]. IFNγ deficient mice are resistant to the development of AA [70] and blockade of IFNγ prevented AA onset and reduced accumulation of CD8 + NKG2D + T cells in AA mouse skin [16,68], suggesting an approach to abrogate the IFNγ signaling in CD8 + T cells could be a therapy for AA. Targeting of other proinflammatory cytokines may also be effective.…”

Section: Targeting Cytokine Signalingmentioning

confidence: 99%

The role of lymphocytes in the development and treatment of alopecia areata

Guo

Cheng

Shapiro

et al. 2015

Expert Review of Clinical Immunology

View full text Add to dashboard Cite

SummaryAlopecia areata (AA) development is associated with both innate and adaptive immune cell activation, migration to peri-and intra-follicular regions, and hair follicle disruption. Both CD4+ and CD8+ lymphocytes are abundant in AA lesions; however, CD8+ cytotoxic T lymphocytes are more likely to enter inside hair follicles, circumstantially suggesting that they have a significant role to play in AA development. Several rodent models recapitulate important features of the human autoimmune disease and demonstrate that CD8+ cytotoxic T lymphocytes are fundamentally required for AA induction and perpetuation. However, the initiating events, the selfantigens involved, and the molecular signaling pathways, all need further exploration. Studying CD8+ cytotoxic T lymphocytes and their fate decisions in AA development may reveal new and improved treatment approaches.

show abstract

Alopecia Areata Induced in C3H/HeJ Mice by Interferon-Gamma: Evidence for Loss of Immune Privilege

Cited by 84 publications

References 7 publications

Lymphocytes, neuropeptides, and genes involved in alopecia areata

Lymphocytes, neuropeptides, and genes involved in alopecia areata

Controlled Delivery of T-box21 Small Interfering RNA Ameliorates Autoimmune Alopecia (Alopecia Areata) in a C3H/HeJ Mouse Model

The role of lymphocytes in the development and treatment of alopecia areata

Contact Info

Product

Resources

About