Spleen contributes to chronic restraint stress-induced lung injury through splenic CD11b⁺ cells

Chronic stress can induce lung injury. The spleen, as the largest peripheral immune organ, plays a crucial role in various lung diseases. Our previous study found that the spleen underwent significant changes during chronic restraint stress (CRS). However, the exact role of the spleen in CRS-induced lung injury remains unclear. In this study, we found that CRS could increase lung index. CRS could lead to alterations of the lungs such as destruction of alveolar wall, thickening of alveolar septa, dilation of pulmonary capillaries, and increased inflammatory cell infiltration. CRS increases the concentration of malondialdehyde (MDA), decreases the level of surfactant protein A (SP-A), and elevates the levels of pro-inflammatory factors (TNF-α, IL-6, and IL-1β) in the lungs. Additionally, CRS could increase the proportions and numbers of CD11b⁺Ly6C^hiLy6G^- monocytes in the lung, while cannot alter proportions and numbers of CD3^-NK1.1⁺ NK cells, CD3⁺CD4⁺ T cells, CD3⁺CD8⁺ T cells, and CD11b⁺Ly6G⁺ neutrophils. Moreover, the levels of inflammatory markers in lung tissues were positively correlated with the proportion of CD11b⁺Ly6C^hiLy6G^- monocytes. Interestingly, splenectomy inhibited CRS-induced lung injury and attenuated the alteration in the proportion of CD11b⁺Ly6C^hiLy6G^- monocytes in the lungs induced by CRS. Moreover, splenic CD11b⁺ cells, rather than splenic CD11b^- cells, transfused into splenectomized mice, and subsequently exposed to CRS, can cause lung injury. These results suggest that CRS could induce lung injury and CD11b⁺Ly6C^hiLy6G^- monocytes aggregation in the lung. The spleen could contribute to CRS-induced lung injury. Furthermore, splenic CD11b⁺ cells might play an important role in CRS-induced lung injury.