Hosoda Tomoko, Mito Natsuko, Yoshino Haruka, Sato Kazuto
Department of Food and Nutrition, Japan Women's University, Tokyo, Japan.
Int Arch Allergy Immunol. 2004 Jan;133(1):19-28. doi: 10.1159/000075250. Epub 2003 Nov 28.
Estrogen plays an important modulatory role in the immune system, and is concerned with the pathophysiology of autoimmune diseases such as rheumatoid arthritis (RA), although the mechanism has not yet been clarified. Oral tolerance, a form of specific peripheral tolerance, which is recognized as a new therapeutic strategy, is related to the function of gut-associated lymphoid tissue.
In this study, using collagen-induced arthritis as an animal model of RA, the effects of 17beta-estradiol (E2) on oral tolerance induction were investigated. For induction of oral tolerance, mice were fed 60 microg type II collagen (CII) for 10 consecutive days prior to each CII immunization. Mice in the E2 treatment groups were injected with 5 microg (low dose) or 500 microg (high dose) E2 three times during the induction of oral tolerance.
Oral tolerance induction suppressed the occurrence of arthritis, the proliferative response of splenocytes to CII and the specific DTH response. However, E2 treatment abrogated the suppression, which might be connected with a change in function of Peyer's patch (PP) lymphocytes.
These results suggest that oral tolerance induction might be affected by estrogen treatment through alteration of intestinal immune responses.
雌激素在免疫系统中发挥重要的调节作用,并且与类风湿关节炎(RA)等自身免疫性疾病的病理生理学相关,尽管其机制尚未阐明。口服耐受作为一种特异性外周耐受形式,被认为是一种新的治疗策略,与肠道相关淋巴组织的功能有关。
在本研究中,以胶原诱导的关节炎作为RA的动物模型,研究17β-雌二醇(E2)对口服耐受诱导的影响。为诱导口服耐受,在每次用II型胶原(CII)免疫前,给小鼠连续10天喂食60微克CII。在口服耐受诱导期间,E2治疗组的小鼠注射5微克(低剂量)或500微克(高剂量)E2三次。
口服耐受诱导抑制了关节炎的发生、脾细胞对CII的增殖反应以及特异性迟发型超敏反应(DTH)。然而,E2治疗消除了这种抑制作用,这可能与派伊尔结(PP)淋巴细胞功能的改变有关。
这些结果表明,雌激素治疗可能通过改变肠道免疫反应影响口服耐受诱导。