Maternal IL-6 can cause T-cell-mediated juvenile alopecia by non-scarring follicular dystrophy in mice.
Maternal IL-6 can cause T-cell-mediated juvenile alopecia by non-scarring follicular dystrophy in mice.
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DOI：
10.1111/exd.12914
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发表时间：
2016-03
影响因子：
3.6
通讯作者：
Schrum AG
中科院分区：
文献类型：
--
作者：
Smith SE;Maus RL;Davis TR;Sundberg JP;Gil D;Schrum AG
为了破译自身免疫性疾病斑秃 (AA) 的免疫学机制，我们假设白介素 6 (IL-6) 可能与青少年发病的 AA 相关，但目前尚无实验模型。在怀孕雌性 C57BL/6 (B6) 小鼠中进行肌内转基因过度表达 IL-6 后，我们发现后代表现出最初正常且完整的幼年毛发生长周期，但在出生后第 18 天左右出现脱发。这种脱发是斑片状且可逆的（非疤痕性），并且与 Ulbp1 表达上调有关，Ulbp1 是人类 AA 相关 ULBP3 基因的唯一小鼠同源物。脱发还与淋巴细胞（包括 α-β T 细胞）对毛囊的炎症浸润有关，这会导致表面脱发。尽管这些明显与 AA 具有共同特征，但病变以毛囊营养不良为主，这不是人类 AA 疾病的典型特征，具有与 B6 脱发和皮炎一致的一些特征。此外，青少年发病的脱发后，表面毛发完全、自发恢复，而没有复发脱发。延长暴露于 IL-6 会延长恢复时间，但一旦恢复，重复从头暴露于高剂量 IL-6 不会再次诱发脱发。这些数据表明，虽然大量的分子和细胞途径可能是共享的，但功能相似的脱发疾病可以通过不同的病理机制发生。
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.
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DOI：
10.4049/jimmunol.1100657
发表时间：
2012-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Alli R;Nguyen P;Boyd K;Sundberg JP;Geiger TL
通讯作者：
Geiger TL
影响因子：
10.5
作者：
Du, Yang;Yang, Marie;Wan, Yihong
通讯作者：
Wan, Yihong
影响因子：
6.5
作者：
Sundberg, JP;Silva, KA;King, LE
通讯作者：
King, LE
影响因子：
6.5
作者：
Freyschmidt-Paul, P;Seiter, S;Hoffmann, R
通讯作者：
Hoffmann, R
DOI：
10.1006/bbrc.2000.2364
发表时间：
2000-03-24
影响因子：
3.1
作者：
Sano, M;Fukuda, K;Ogawa, S
通讯作者：
Ogawa, S