Atochina Olga, Harn Donald
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
Exp Dermatol. 2006 Jun;15(6):461-8. doi: 10.1111/j.1600-0625.2006.00431.x.
The helminth glycan LNFPIII is an immunomodulatory molecule, driving CD4(+) Th2-type biasing as well as immune suppression. Psoriasis is an autoimmune disease where the immune mechanisms as well as the antigens responsible for development of immune autoreactivity are still not known. In the absence of defined immunological mechanisms, we asked whether LNFPIII would function as novel therapy for psoriasis. We tested the therapeutic efficacy of LNFPIII using the flaky skin (fsn)/fsn mutant mouse model of psoriasis-like lesion development. We found that treatment of mice with LNFPIII prevented the appearance of psoriatic skin lesions on fsn/fsn mice. Examination of the skin 2 weeks after treatment demonstrated that prevention of skin lesions was associated with maintenance of normal epidermis thickness in LNFPIII-treated mice as compared with a significantly thickened epidermis in control treated and diseased mice. In addition, cells from skin of LNFPIII-treated mice produced lower amounts of interferon-gamma as compared with cells from skin of control treated diseased mice. Examination of macrophages and T cells from peripheral lymph nodes of control and LNFPIII-treated fsn/fsn mice showed that glycan treatment reduced the numbers of Gr1(+)F4/80(+) macrophages and the numbers of CD8(+) T cells, restoring the numbers of these two cell populations as well as the CD4 : CD8 ratio to near normal levels. Overall, the results from this study suggest that the helminth immunomodulatory glycan LNFPIII functions to prevent development of psoriatic-like skin lesions in fsn/fsn mice.
蠕虫聚糖LNFPIII是一种免疫调节分子，可驱动CD4(+) Th2型偏向以及免疫抑制。银屑病是一种自身免疫性疾病，其免疫机制以及导致免疫自身反应性发展的抗原仍不清楚。在缺乏明确免疫机制的情况下，我们探究了LNFPIII是否可作为银屑病的新型治疗方法。我们使用银屑病样病变发展的片状皮肤（fsn）/fsn突变小鼠模型测试了LNFPIII的治疗效果。我们发现用LNFPIII治疗小鼠可预防fsn/fsn小鼠出现银屑病皮肤病变。治疗2周后对皮肤进行检查发现，与对照治疗和患病小鼠中明显增厚的表皮相比，LNFPIII治疗的小鼠中皮肤病变的预防与正常表皮厚度的维持有关。此外，与对照治疗的患病小鼠皮肤中的细胞相比，LNFPIII治疗的小鼠皮肤中的细胞产生的干扰素-γ量更低。对对照和LNFPIII治疗的fsn/fsn小鼠外周淋巴结中的巨噬细胞和T细胞进行检查发现，聚糖治疗减少了Gr1(+)F4/80(+)巨噬细胞的数量以及CD8(+) T细胞的数量，使这两种细胞群体的数量以及CD4:CD8比率恢复到接近正常水平。总体而言，这项研究的结果表明，蠕虫免疫调节聚糖LNFPIII可预防fsn/fsn小鼠中银屑病样皮肤病变的发展。
