Rearrangement of actin cytoskeleton correlates significantly with the immune responses as the perturbation of cytoskeletal dynamics leads to many immune deficiencies. Mechanistic insights into this correlation remain unknown. Cellular spreading, the most characteristic phenotype associated with monocyte to macrophage differentiation, led us to investigate the contribution of actomyosin dynamics in monocyte differentiation. Our observation revealed that actomyosin reorganization intrinsically governs the process of monocyte to macrophage differentiation. Further, we established that the MAPK-driven signaling pathways regulate the cellular actomyosin dynamics that direct monocyte to macrophage differentiation. We also identified P42/44 Mitogen-Activated Protein Kinase (P42/44 MAPK), P38 Mitogen-Activated Protein Kinase (P38 MAPK), MAP Kinase Activated Protein Kinase 2 (MK-2), Heat Shock Protein 27 (Hsp-27), Lim Kinase (Lim K), non-muscle cofilin (n-cofilin), Myosin Light Chain Kinase (MLCK) and Myosin Light Chain (MLC) as critical components of the signaling network. Moreover, we have shown the involvement of the same signaling cascade in 3D gel-like microenvironment induced spontaneous monocyte to macrophage differentiation and in human blood-derived PBMC differentiation. Our study reveals new mechanistic insights into the process of monocyte to macrophage differentiation.

肌动蛋白细胞骨架的重排与免疫反应显着相关，因为细胞骨架动力学的扰动会导致许多免疫缺陷。对这种相关性的机制见解仍然未知。细胞扩散是与单核细胞到巨噬细胞分化相关的最具特征的表型，使我们研究了肌动球蛋白动力学在单核细胞分化中的贡献。我们的观察表明，肌动球蛋白重组本质上控制着单核细胞向巨噬细胞分化的过程。此外，我们确定 MAPK 驱动的信号通路调节细胞肌动球蛋白动力学，该动力学指导单核细胞向巨噬细胞分化。我们还鉴定了 P42/44 丝裂原激活蛋白激酶 (P42/44 MAPK)、P38 丝裂原激活蛋白激酶 (P38 MAPK)、MAP 激酶激活蛋白激酶 2 (MK-2)、热休克蛋白 27 (Hsp-27)、Lim 激酶 (Lim K)、非肌纤维蛋白 (n-cofilin)、肌球蛋白轻链激酶 (MLCK) 和肌球蛋白轻链(MLC) 作为信号网络的关键组件。此外，我们已经表明相同的信号级联参与了 3D 凝胶样微环境诱导的自发单核细胞向巨噬细胞分化和人血衍生的 PBMC 分化。我们的研究揭示了对单核细胞到巨噬细胞分化过程的新机制见解。我们已经证明了在 3D 凝胶样微环境诱导的自发单核细胞向巨噬细胞分化和人血源性 PBMC 分化中涉及相同的信号级联。我们的研究揭示了对单核细胞到巨噬细胞分化过程的新机制见解。我们已经证明了在 3D 凝胶样微环境诱导的自发单核细胞向巨噬细胞分化和人血源性 PBMC 分化中涉及相同的信号级联。我们的研究揭示了对单核细胞到巨噬细胞分化过程的新机制见解。