Intervention with oral lactococcus lactis expressing CfaE (LL-CfaE) prevents or treats Sjogren’s Syndrome (SjS)-like disease in mice 3025

Abstract Description SjS is a chronic, progressive autoimmune disease, occurring primarily in postmenopausal women, marked by inflammatory cell infiltration of the salivary and lacrimal glands. To date, no vaccine or therapeutic exists to cure SjS, and patients must rely on lifelong therapies to treat symptoms. Past studies have shown that oral treatment with the adhesin from E. coli CFA/I fimbriae confers protection against SjS using a L. lactis strain expressing CFA/I fimbriae (LL-CFA/I). We hypothesized that the regulatory activity imparted by CFA/I fimbriae is contained within CfaE. Thus, L. lactis was adapted to express the tip protein from CFA/I fimbriae (LL-CfaE). To test this hypothesis, bone marrow-derived dendritic cells (BMDCs) infected with LL-CfaE or LL-CFA/I showed increased IL-10 and TGF-ß production. Groups of C57BL/6.NOD-Aec1Aec2 mice, which spontaneously develop SjS and gradually lose saliva secretion, were treated at 3-wk intervals beginning at 6 wks of age. Reductions in saliva flow rates were attenuated in LL-CfaE-treated mice relative to PBS- or LL vector-treated mice. To test its therapeutic potential, LL-CfaE treatments beginning at 21 wks of age also significantly attenuated loss of saliva flow rates. Such treatments reduced salivary gland pathology and enhanced regulatory T cells to limit salivary gland inflammation. These data show that orally dosing with LL-CfaE limits SjS progression via activation of Tregs, and provide the basis for future testing in SjS patients. Funding Sources Work supported by NIH DE026450. Topic Categories Mucosal and Regional Immunology (MUC)