Sex-related differences in autoimmune-induced lung lesions in MRL/MpJ-fas^lpr mice are mediated by the development of mediastinal fat-associated lymphoid clusters

Abstract

MRL/MpJ-Fas^lpr (lpr) mice are a model for autoimmune diseases such as systemic lupus erythematosus (SLE). These diseases mainly affect women, with a 10:1 female-to-male ratio, and cause pleuropulmonary lesions. We previously revealed a correlation between mediastinal fat-associated lymphoid cluster (MFALC) development and cellular infiltration in the lungs of lpr male mice; however, we did not report on MFALCs in females. The purpose of this investigation was to reveal sex-related differences in MFALCs in lpr mice. We compared the morphological features of MFALCs and lung mononuclear cell aggregates (LMCAs) in 5-month-old male and female lpr mice. The females showed significantly elevated anti-dsDNA autoantibody titers and larger MFALCs, with a higher ratio of lymphatic vessel (LV) and high endothelial venule (HEV) areas to MFALC area, and greater numbers of T- and B-cells, macrophages, and proliferating and dendritic cells in MFALCs and LMCAs than males. Our data indicated that MFALCs were more developed and lung lesions were more severe in female than in male lpr mice, thereby suggesting a potential role for LVs and HEVs in the establishment of MFALCs and lung lesions. Further investigation in female lpr mice will be needed for treatment of human respiratory diseases and autoimmune disorders.

Keywords:

• Autoimmune disease mouse models
• lung
• mediastinal fat-associated lymphoid cluster
• pleuropulmonary lesions
• sex-related differences

Disclosure statement

This article has not been published or presented elsewhere in part or in entirety, and is not under consideration by another journal. All authors have approved the article and agree with submission to this journal. There are no conflicts of interest to declare.

Additional information

Funding

This work was supported in part by funding from the Japan Society for the Promotion of Science, postdoctoral fellowship (JSPS, Number 14F04400); and the Hokkaido University tenure track program.