Comparative analysis of mediastinal fat‐associated lymphoid cluster development and lung cellular infiltration in murine autoimmune disease models and the corresponding normal control strains

Abstract

SummaryWe previously discovered mediastinal fat-associated lymphoid clusters (MFALCs) as novel lymphoid clusters associated with mediastinal fat tissue in healthy mice. However, no data about their morphology in immune-associated disease conditions, and their relationship with lung infiltration, is available to date. In the present study, we compared the morphological features of MFALCs in 4-month-old male murine autoimmune disease models (MRL/MpJ-lpr mice and BXSB/MpJ-Yaa mice) with those of the corresponding control strains (MRL/MpJ and BXSB/MpJ, respectively). In addition, we analysed their correlation with lung infiltration. Furthermore, immunohistochemistry for CD3, B220, Iba1, Gr1 and BrdU was performed to detect T cells and B cells, macrophages, granulocytes and proliferating cells, respectively. The spleen weight to body weight ratios and anti-double-stranded DNA autoantibody titres were found to be significantly higher in the autoimmune models than in the control strains. Furthermore, the autoimmune model presented prominent MFALCs, with a significantly greater ratio of lymphoid cluster area to total mediastinal fat tissue area, and more apparent diffused cellular infiltration into the lung lobes than the other studied strains. Higher numbers of T and B cells, macrophages and proliferating cells, but fewer granulocytes, were observed in the autoimmune models than in the control strains. Interestingly, a significant positive Pearson's correlation between the size of the MFALCs and the density of CD3-, B220-and Iba1-positive cells in the lung was observed. Therefore, our data suggest a potentially important role for MFALCs in the progression of lung disease. However, further investigation is required to clarify the pathological role of MFALCs in lung disease, especially in inflammatory disorders.

Profiling of cellular immune responses to Mycoplasma pulmonis infection in C57BL/6 and DBA/2 mice

“…This result was similar to the result in murine auto-immune disease models (16). The increase in the ratio might be caused by over expression of cytokines that induce the proliferation of immune cells in MFT area of D2 mice.…”

Histopathological Correlations between Mediastinal Fat-Associated Lymphoid Clusters and the Development of Lung Inflammation and Fibrosis following Bleomycin Administration in Mice

“…In a recent study, we demonstrated better developed MFALCs in two mic model of autoimmune disease (MRL/MpJ-lpr and BXSB/MpJ-Yaa) that show a phenotype similar to human SLE as compared to control strains. In addition, we reported significantly positive correlation between the size of LCs and lung infiltration in mice with autoimmune diseases, suggesting that MFALCs may play a role in progression of lung lesions ( 10 ). Moreover, it has been recently revealed that the size of mesenteric FALCs increases following induction of peritonitis in mice ( 19 ).…”

“…Additionally, our previous report has shown significant positive correlations between immune cell infiltration into the lungs in two animal models of autoimmunity that develop a phenotype similar to human systemic lupus erythematosus (SLE) and the size of novel lymphoid clusters (LCs) associated with mediastinal fat tissues (MFTs) that termed as mediastinal fat-associated lymphoid cluster (MFALCs). Therefore, our previous studies suggested a possible role for such MFALCs in the progression of lung diseases ( 10 , 11 ). However, further investigation is required to clarify the pathological role of MFALCs in lung diseases, especially those with an inflammatory nature.…”

Fat-Associated Lymphoid Clusters in Inflammation and Immunity

“…A recent report has shown that medFALC are present in large numbers in two animal models of autoimmunity that develop a phenotype similar to human systemic lupus erythematosus (SLE) (49). The MRL/MpJ-lpr mouse model carries a mutation in the gene encoding Fas, a cell membrane receptor that induces caspase activation and apoptosis.…”

“…The BXSB/MpJ-Yaa mice developed systemic autoimmunity, with males being more affected due to a locus called autoimmune accelerator located in the Y chromosome. Both strains showed large medFALCs size that correlated with a significant increased level of immune cell infiltration in the lungs with respect to their control strains (49). It will be interesting to assess whether medFALCs in the MRL/MpJ-lpr model contained anti dsDNA Ab-forming B cells.…”