CD4 T cell specifically deplete tissue resident alveolar macrophage 2310198

Abstract

Abstract Introduction Alveolar macrophages are lung tissue resident macrophages that play a critical role clearing particles, protecting from infectious agent and inflammation. Aberrancy in the development or homeostasis of alveolar macrophage leads to lung inflammation. In the present study we tried to decipher the role of CD4 T cells in alveolar macrophage depletion and lung inflammation in kinase dead IKKa knock-in K44A (KA/KA) mice. Methods we used flow cytometry, adoptive CD4 T cells transfer and real time PCR Results We observed significant depletion of alveolar macrophages (CD11c+Siglecf+) in KA/KA mice. We thought the depletion of alveolar macrophage may be a non-specific macrophage disappearance reaction (MDR) as KA/KA lung has type II inflammation marked by increase Il4, Il13, Il5, Il33, Retnla, and Ym1 expression. We further observed the expression of Csf2 and Tgfb1 genes encoding GM-CSF and TGF-beta respectively that play a critical role in alveolar macrophage development and homeostasis were significantly reduced in KA/KA mice suggesting that the alveolar macrophage depletion is not an MDR. Not to our surprise, in KA/KA mice, we found significant reduction in the expression of Pparg gene that encodes transcription factor PPAR-gamma activated by GM-CSF and TGF-beta critical in alveolar macrophage development. Interestingly we observed no changes in the percentage of alveolar macrophages in the lungs of KA/KA; Cd4-/- as well as KA/KA; Rag-/- mice compared with wild type mice suggesting that the CD4 T cells may play a critical role in alveolar macrophage depletion. Further we observed significant depletion of alveolar macrophage in the lungs of KA/KA; Rag-/- mice that were adoptively transferred with KA/KA CD4 T cells, substantiating the role CD4 T cells in alveolar macrophage depletion. Conclusion In conclusion, CD4 T cells specifically deplete tissue resident alveolar macrophage by reducing the expression of Csf2, Tgfb1 and Pparg leading to lung inflammation in kinase dead IKKa (K44A) mice. Funding Source n/a Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)