Department of Immunology, University of Manchester, Manchester, UK.
Hum Immunol. 2010 Apr;71(4):372-6. doi: 10.1016/j.humimm.2010.01.018. Epub 2010 Feb 4.
Toll-like receptors (TLRs) are important in the initiation of immune responses in both health and disease. How TLR activity alters with age, gender, and also with immunosuppressive agents is still largely unexplored. We studied TLR activity in 49 healthy individuals as well as in 26 patients receiving immunosuppressive drugs. TLR activity did not alter significantly between the ages of 2 and 67 years. However, females had twice the TLR7 ligand-induced interferon-I response of males (OR [95% CI] 2.7 [1.4-5.1]), whereas TLR3 and four activities were not significantly different between the sexes. The T-cell immunosuppressant agents cyclosporine, tacrolimus, and azathioprine, as well as low dose glucocorticosteroids did not significantly alter TLR pathway responses. In contrast, high dose glucocorticosteroids reduced in vivo TLR responses by 70%-90%. We suggest that gender differences in TLR responses may help to explain the female preponderance of some autoimmune disorders. Furthermore, an understanding the effects of immunosuppressive agents on TLR-pathway activity should allow more focused therapy for autoimmune disorders.
Toll 样受体 (TLRs) 在健康和疾病状态下的免疫反应起始中具有重要作用。TLR 活性如何随年龄、性别以及免疫抑制剂的变化而变化，在很大程度上仍未得到探索。我们研究了 49 名健康个体以及 26 名接受免疫抑制剂治疗的患者的 TLR 活性。TLR 活性在 2 岁至 67 岁之间没有显著变化。然而，女性的 TLR7 配体诱导干扰素-I 反应是男性的两倍（OR [95%CI] 2.7 [1.4-5.1]），而 TLR3 和四种活性在性别之间没有显著差异。T 细胞免疫抑制剂环孢素、他克莫司和硫唑嘌呤以及小剂量糖皮质激素对 TLR 通路反应没有显著影响。相比之下，大剂量糖皮质激素使体内 TLR 反应降低了 70%-90%。我们认为，TLR 反应的性别差异可能有助于解释某些自身免疫性疾病中女性居多的现象。此外，了解免疫抑制剂对 TLR 通路活性的影响，应该可以为自身免疫性疾病提供更有针对性的治疗。
