Pathological Alternations of Mediastinal Fat-Associated Lymphoid Cluster and Lung in a Streptozotocin-Induced Diabetic Mouse Model

Abstract

Diabetes is a devastating global health problem and is considered a predisposing factor for lung injury progression. Furthermore, previous reports of the authors revealed the role of mediastinal fat-associated lymphoid clusters (MFALCs) in advancing respiratory diseases. However, no reports concerning the role of MFALCs on the development of lung injury in diabetes have been published. Therefore, this study aimed to examine the correlations between diabetes and the development of MFALCs and the progression of lung injury in a streptozotocin-induced diabetic mouse model. Furthermore, immunohistochemical analysis for immune cells (CD3+ T-lymphocytes, B220+ B-lymphocytes, Iba1+ macrophages, and Gr1+ granulocytes), vessels markers (CD31+ endothelial cells and LYVE-1+ lymphatic vessels “LVs”), and inflammatory markers (TNF-α and IL-5) was performed. In comparison to the control group, the diabetic group showed lung injury development with a significant increase in MFALC size, immune cells, LVs, and inflammatory marker, and a considerable decrease of CD31+ endothelial cells in both lung and MFALCs was observed. Furthermore, the blood glucose level showed significant positive correlations with MFALCs size, lung injury, immune cells, inflammatory markers, and LYVE-1+ LVs in lungs and MFALCs. Thus, we suggest that the development of MFALCs and LVs could contribute to lung injury progression in diabetic conditions.

Possible Crosstalk of the Immune Cells within the Lung and Mediastinal Fat-Associated Lymphoid Clusters in the Acute Inflammatory Lung Asthma-Like Mouse Model

“…Despite the presence of several reports concerning the role of several immune cells (T-and B-lymphocytes and macrophages) [10][11][12][13] and the lung NHC [7] in the pathogenesis of lung asthma progression, the possible source of the recruitment of immune cells in the asthmatic mouse model is still poorly understood. Currently, we revealed the correlation between the development of MFALCs and pathogenesis of several lung injuries and immune cell infiltration into the lung using several mouse models, including genetic autoimmune mouse model [21,29] with the septic condition such as bleomycin-induced pneumonitis mouse model [22], the aseptic condition such as Mycoplasma pulmonis infection in mice [30], and metabolic disorders such as streptozotocininduced diabetic mouse model [31]. However, the functional attribution of MFALCs in either asthma progression or recovery is not yet clarified.…”

Dual Effect of Bleomycin on Histopathological Features of Lungs and Mediastinal Fat-Associated Lymphoid Clusters in an Autoimmune Disease Mouse Model

“…The details of antigen retrieval and optimal primary antibody dilutions are summarized in Table 1 . Additionally, the lung sections of different studied groups were stained with rabbit polyclonal anti-collagen I antibody, and anti-COL3A1 to detect degree of collagen depositions for different collagen types according to our recent report ( 20 ). Furthermore, double immunofluorescence staining was performed to reveal the occurrence of B220 + B cells and CD3 + T cells in both MFALCs and the lungs of different groups in both studied strains.…”

“…The ratio of lymphoid clusters (LCs) area/total MFTs area was calculated from the H&E-stained digital images using the ImageJ software (ver. 1.32j, http://rsb.info.nih.gov/ij), as described in our previous reports (7,20). Furthermore, the extent of lung injury was measured using images of MT-stained lung sections from grade 0 to 8 according to the scoring criteria reported by Ashcroft et al (21), and the average of such scores per mouse was recorded.…”

Histopathological Impact of Bleomycin on Lung Injury and Development of Mediastinal Fat-Associated Lymphoid Clusters in the Lymphoproliferative Mouse Model

“…Lung fibrosis is developed in most of the chronic pulmonary diseases and is the major cause of mortality worldwide (de Hilster et al, 2019). Interestingly, we have reported a close relationship between the development of novel lymphoid clusters (termed as mediastinal fat-associated lymphoid clusters "MFALCs") and the progression of lung injury in several mouse models including genetically mutated mouse strains (such as MRL/MpJ-Fas lpr/lpr "Lpr" and BXSB/MpJ-Yaa "Yaa" autoimmune mouse models) (Elewa et al, 2016), or following either septic (Elewa et al, 2018(Elewa et al, , 2021c or aseptic (Boonyarattanasoonthorn et al, 2019) induction of pneumonitis. Both Lpr and male Yaa mouse are autoimmune disease mouse models that showed more developed MFALCs and lung injury in comparison to their control strains (Elewa et al, 2016).…”