Abstract

Recently, we clarified the function of mediastinal fat-associated lymphoid clusters (MFALCs) in the progression of several respiratory diseases. However, their role has not yet been identified in the lung asthmatic condition. Hence, we compared the immune cells in lung and MFALCs of C57BL/6N mice on days 3 and 7 following intranasal instillation of either papain (papain group “PG”) or phosphate buffer saline (PBS) (vehicle group “VG”). The PG showed significantly prominent MFALCs, numerous goblet cells (GCs), and higher index ratios of different immune cells (macrophages, natural helper cells (NHC), B- and T-lymphocytes) within the MFALCs and lung than in the VG on both days 3 and 7. Interestingly, a tendency of decreased size of MFALCs and a significant reduction in the number of GCs and immune cells were observed within the MFALCs and lung in the PG on day 7 than on day 3. Furthermore, the quantitative parameters of these immune cells in MFALCs were significantly and positively correlated with the size of MFALCs and immune cells in the lung. This suggested that the possible crosstalk between immune cells within MFALCs and the lung could play a critical role in the progression and recovery of the acute inflammatory lung asthma.

Highlights

  • It has been clarified that infiltration of immune cells into the lung plays a critical role in the development of asthma followed by irritation in the airway [10,11]. The role of both T and B cells has been clarified in most mouse models that simulate asthma [12,13], recent studies have revealed the involvement of non-T and non-B innate lymphoid cells (ILCs) in the asthma development in the Rag-deficient mice lacking T and B cells following the administration of papain [14]

  • We reported a significant increase in mediastinal fat-associated lymphoid clusters (MFALCs)’ size and the number of immune cells in bronchoalveolar lavage fluid (BALF), MFALCs, and lung lobes in papain group than that found in the vehicle group on both days 3 and 7

  • We revealed positive correlations between the immune cell population in MFALCs with that of the population in lung tissue

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Summary

Introduction

The role of both T and B cells has been clarified in most mouse models that simulate asthma [12,13], recent studies have revealed the involvement of non-T and non-B innate lymphoid cells (ILCs) in the asthma development in the Rag-deficient mice lacking T and B cells following the administration of papain [14]. The role of lung natural helper cells (NHC) as novel ILCs group (ILC2s) has been reported as a rapid T cell-independent source of Th2 cell-type cytokines population in papain-induced asthma mouse model [7,18]. T-lymphocytes) and innate (macrophages and NHC) populations within the MFALCs in the progression and recovery of asthma in C57BL/6N (B6) mice following a single intranasal (i.n.) instillation of either papain (papain group) or PBS (vehicles group). Such correlations showed significant values for B-lymphocytes, macrophages, and NHC but not for T-lymphocytes, suggesting possible crosstalk between the former immune cell populations within lung and MFALCs in either progression or recovery of the asthmatic condition

Indices of Asthma Induction in the Mice Model
Morphological
Morphological and Morphometrical Analysis of Lung Tissue among the Studied
Analysis of Immune
Analysis of the Occurrence
Histopathological
Discussion
Materials and Methods
Experimental Design
BALF Collection and Preparation for Cytological Interpretation
Morphological and Histopathological Analysis
Immunohistochemical Staining of High Endothelial Venules and Immune Cells
Immunofluorescent Staining of NHC
Histomorphometric Measurements
Statistical Analysis
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