Autoimmune hair loss (alopecia areata) transferred by T lymphocytes to human scalp explants on SCID mice.

Gilhar, Amos; Ullmann, Yehuda; Berkutzki, T; Assy, Bedia; Kalish, Richard S.

doi:10.1172/jci551

Cited by 225 publications

(203 citation statements)

References 22 publications

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“…IL-1R1 is known as a potent regulator of ICAM-1, 42 which in turn is implicated in regulation of adhesion and proliferation of skin lymphocytes and follicular keratinocytes 43,44 and is associated with some HF pathological conditions in humans, such as alopecia areata. 45,46 These results further support the idea that hairless mice are an attractive model for elucidating the molecular controls of normal and pathological catagen-associated DP movement.…”

Section: Discussionsupporting

confidence: 66%

The Role of the Hairless (hr) Gene in the. Regulation of Hair Follicle Catagen Transformation

Panteleyev¹,

Botchkareva²,

Sundberg³

et al. 1999

The American Journal of Pathology

153

136

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Mice that carry a mutation at the hairless (hr) locus develop seemingly normal hair follicles (HF) but shed their hairs completely soon after birth. Histologically , their HFs degenerate into characteristic utriculi and dermal cysts shortly after the entry of the HF into the first regression phase (catagen) , during the initiation of HF cycling. Here , we show that at least nine distinct stages of HF disintegration can be distinguished in hr/hr mice. Toward the end of HF morphogenesis (day 15 postpartum) the proximal hair bulb in hr/hr skin undergoes premature and massive apoptosis. This is associated with a dyscoordination of cell proliferation in defined HF compartments, malpositioning of the proximal inner root sheath, striking atrophy of outer root sheath , and failure of trichilemmal keratinization in the developing club hair. Rather than undergoing their normal catagenassociated involution , the hair bulb and central outer root sheath disintegrate into separate cell clusters, thus disrupting all epithelial contact with the dermal papilla. Dermal papilla fibroblasts fail to migrate upward , and break up into clusters of shrunken cells stranded in the reticular dermis as dermal cyst precursors , while the upper HF epithelium transforms into utriculi. Some dermal papilla cells , which normally never undergo apoptosis , also become TUNEL؉ in hr/hr skin , and their normally high expression of a key adhesion molecule , neural cell adhesion molecule , declines. Thus , loss of a functional hr gene product (a putative zinc finger transcription factor) initiates a premature , highly dysregulated catagen, which results in the destruction of the normal HF architecture and abrogates the HF's ability to cycle. This provides new insights into the pathobiology of the hr mutation , and suggests that the normal hr gene product is a crucial element of catagen control. (Am J Pathol 1999, 155:159 -171)

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Section: Discussionsupporting

confidence: 66%

The Role of the Hairless (hr) Gene in the. Regulation of Hair Follicle Catagen Transformation

Panteleyev¹,

Botchkareva²,

Sundberg³

et al. 1999

The American Journal of Pathology

153

136

View full text Add to dashboard Cite

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“…3 Although the exact etiology of AA is still unknown, there is accumulated evidence that supports a hereditary susceptibility and an autoimmune pathogenesis, such as a familial history in 4-27%, 4,5 and the increased frequency of other autoimmune diseases, particularly autoimmune thyroid disease, and of organspecific autoantibodies in patients with AA [6][7][8] as well as the presence of CD8 + T cells next to the hair follicles. 9,10 Among the various immunomodulatory treatments that have been used to induce remission in AA, systemic corticosteroids have been administered in extensive or rapidly progressive AA and in alopecia totalis/universalis. 11,12 Systemic oral corticosteroids have been reported to be effective in extensive AA, but relapses occurred when the dosage was reduced.…”

Section: Introductionmentioning

confidence: 99%

Medium-dose prednisolone pulse therapy in alopecia areata

Efentaki¹,

Altenburg²,

Haerting³

et al. 2009

Dermato-Endocrinology

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“…T lymphocytes from the patients could cause alopecia areata, when cultured with hair follicle homogenate along with antigen-presenting cells and injected into the skin explants on severe combined immunodeficiency mice. 3 Purified T cell injection experiments result suggested that both CD4-and CD8-positive T cells have a role in pathogenesis of alopecia areata, CD8-positive cells acting as the main effector cells with the regulatory control by CD4-positive T cells. 4 This study was undertaken to clarify whether Th1 CD4 lymphocytes or Th2 CD4 lymphocytes are dominant in the lesions of patients with alopecia areata and also to elucidate the effect of cytokine therapy applying recombinant interleukin-4 (Il4) and neutralizing anti-interferon-␥ (Ifng) antibody into the alopecia areata rodent model C3H/HeJ mice.…”

mentioning

confidence: 99%

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

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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.

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Autoimmune hair loss (alopecia areata) transferred by T lymphocytes to human scalp explants on SCID mice.

Cited by 225 publications

References 22 publications

The Role of the Hairless (hr) Gene in the. Regulation of Hair Follicle Catagen Transformation

The Role of the Hairless (hr) Gene in the. Regulation of Hair Follicle Catagen Transformation

Medium-dose prednisolone pulse therapy in alopecia areata

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

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