Aromatase Controls Sjogren Syndrome-Like Lesions through Monocyte Chemotactic Protein-1 in Target Organ and Adipose Tissue-Associated Macrophages

作者：Iwasa Akihiko; Arakaki Rieko; Honma Naoko; Ushio Aya; Yamada Akiko; Kondo Tomoyuki; Kurosawa Emi; Kujiraoka Satoko; Tsunematsu Takaaki; Kudo Yasusei; Tanaka Eiji; Yoshimura Noriko; Harada Nobuhiro; Hayashi Yoshio; Ishimaru Naozumi^*

来源：American Journal Of Pathology, 2015, 185(1): 151-161.

DOI：10.1016/j.ajpath.2014.09.006

Several autoimmune diseases are known to develop in postmenopausal women. However, the mechanism by which estrogen deficiency influences autoimmunity is unknown. Aromatase is an enzyme that converts androgens to estrogens. Herein, we used female aromatase gene knockout (ArK0) mice as a model of estrogen deficiency to investigate the molecular mechanism that underlies the onset and development of autoimmunity. Histological analyses showed that inflammatory Lesions in the lacrimal and salivary glands of ArK0 mice increased with age. Adoptive transfer of spleen cells or bone marrow cells from ArK0 mice into recombination activating gene 2 knockout mice failed to induce the autoimmune lesions. Expression of mRNA encoding proinflammatory cytokines and monocyte chemotactic protein-1 increased in white adipose tissue of ArK0 mice and was significantly higher than that in wildtype mice. Moreover, an increased number of inflammatory M1 macrophages was observed in white adipose tissue of ArK0 mice. A significantly increased monocyte chemotactic protein-1 mRNA expression of the salivary gland tissue in ArK0 was found together with adiposity. Furthermore, the autoimmune lesions in a murine model of Sjogren syndrome were exacerbated by administration of an aromatase inhibitor. These results suggest that aromatase may play a key role in the pathogenesis of Sjogren syndrome-like lesions by controlling the target organ and adipose tissue-associated macrophage.

• 出版日期2015-1