Division of Agriculture, Department of Poultry Science, University of Arkansas System, Fayetteville, AR, United States.
Front Immunol. 2024 Apr 24;15:1386727. doi: 10.3389/fimmu.2024.1386727. eCollection 2024.
Vitiligo is an acquired de-pigmentation disorder characterized by the post-natal loss of epidermal melanocytes (pigment-producing cells) resulting in the appearance of white patches in the skin. The Smyth chicken is the only model for vitiligo that shares all the characteristics of the human condition including: spontaneous post-natal loss of epidermal melanocytes, interactions between genetic, environmental and immunological factors, and associations with other autoimmune diseases. In addition, an avian model for vitiligo has the added benefit of an easily accessible target tissue (a growing feather) that allows for the repeated sampling of an individual and thus the continuous monitoring of local immune responses over time.
Using a combination of flow cytometry and gene expression analyses, we sought to gain a comprehensive understanding of the initiating events leading to expression of vitiligo in growing feathers by monitoring the infiltration of leukocytes and concurrent immunological activities in the target tissue beginning prior to visual onset and continuing throughout disease development.
Here, we document a sequence of immunologically significant events, including characteristic rises in infiltrating B and αβ T cells as well as evidence of active leukocyte recruitment and cell-mediated immune activities (CCL19, IFNG, GZMA) leading up to visual vitiligo onset. Examination of growing feathers from vitiligo-susceptible Brown line chickens revealed anti-inflammatory immune activities which may be responsible for preventing vitiligo (IL10, CTLA4, FOXP3). Furthermore, we detected positive correlations between infiltrating T cells and changes in their T cell receptor diversity supporting a T cell-specific immune response.
Collectively, these results further support the notion of cell-mediated immune destruction of epidermal melanocytes in the pulp of growing feathers and open new avenues of study in the vitiligo-prone Smyth and vitiligo-susceptible Brown line chickens.
白癜风是一种后天性的色素脱失性疾病,其特征是表皮黑素细胞(产生色素的细胞)在产后丧失,导致皮肤出现白色斑块。Smyth 鸡是唯一一种具有所有人类白癜风特征的白癜风模型,包括:表皮黑素细胞在产后自发丧失、遗传、环境和免疫因素相互作用,以及与其他自身免疫性疾病的关联。此外,白癜风的禽类模型还有一个额外的好处,即有一个容易接近的靶组织(正在生长的羽毛),可以对个体进行重复采样,从而可以随着时间的推移持续监测局部免疫反应。
我们结合流式细胞术和基因表达分析,旨在通过监测在视觉症状出现之前和疾病发展过程中,目标组织中白细胞的浸润和同时发生的免疫活性,全面了解导致生长中的羽毛出现白癜风的起始事件。
在这里,我们记录了一系列具有免疫意义的事件,包括特征性地增加浸润 B 和 αβ T 细胞,以及有证据表明白细胞募集和细胞介导的免疫活性(CCL19、IFNG、GZMA)增加,直至出现视觉白癜风。对易感 Brown 线鸡的生长羽毛进行检查,发现抗炎免疫活性,这可能是预防白癜风的原因(IL10、CTLA4、FOXP3)。此外,我们还检测到浸润 T 细胞与它们的 T 细胞受体多样性变化之间存在正相关,支持 T 细胞特异性免疫反应。
总的来说,这些结果进一步支持了在生长中的羽毛的髓质中,细胞介导的免疫破坏表皮黑素细胞的观点,并为易患白癜风的 Smyth 鸡和易感的 Brown 线鸡开辟了新的研究途径。