Department of Molecular Biosciences, The Wenner-Gren Institute (MBW), Stockholm University, Stockholm, Sweden.
Elife. 2020 Dec 30;9:e64919. doi: 10.7554/eLife.64919.
Postmitotic tissues are incapable of replacing damaged cells through proliferation, but need to rely on buffering mechanisms to prevent tissue disintegration. By constitutively activating the Ras/MAPK-pathway via -overexpression in the postmitotic salivary glands (SGs) of larvae, we overrode the glands adaptability to growth signals and induced hypertrophy. The accompanied loss of tissue integrity, recognition by cellular immunity, and cell death are all buffered by blocking stress signaling through a genuine tissue-autonomous immune response. This novel, spatio-temporally tightly regulated mechanism relies on the inhibition of a feedback-loop in the JNK-pathway by the immune effector and antimicrobial peptide Drosomycin. While this interaction might allow growing SGs to cope with temporary stress, continuous Drosomycin expression in -glands favors unrestricted hypertrophy. These findings indicate the necessity to refine therapeutic approaches that stimulate immune responses by acknowledging their possible, detrimental effects in damaged or stressed tissues.
有丝分裂后组织无法通过增殖来替代受损的细胞，但需要依靠缓冲机制来防止组织解体。通过在幼虫的有丝分裂后唾液腺（SGs）中过度表达来持续激活 Ras/MAPK 通路，我们超越了腺体对生长信号的适应性，并诱导了肥大。伴随而来的组织完整性丧失、细胞免疫识别和细胞死亡，都通过真正的组织自主免疫反应阻断应激信号得到缓冲。这种新颖的、时空上严格调节的机制依赖于免疫效应物和抗菌肽 Drosomycin 抑制 JNK 通路中的反馈环。虽然这种相互作用可能允许生长的 SG 应对暂时的应激，但在 -glands 中持续表达 Drosomycin 有利于不受限制的肥大。这些发现表明，有必要通过承认其在受损或应激组织中的可能有害影响来改进通过刺激免疫反应的治疗方法。
