Department of Medicine - DIMED, University of Padova.
Immunologic and Respiratory Rare Diseases Referral Center, Internal Medicine 1, Ca' Foncello Hospital, Treviso, Italy.
Curr Opin Pulm Med. 2020 Sep;26(5):535-543. doi: 10.1097/MCP.0000000000000711.
The immune determinants of granuloma formation and disease progression in sarcoidosis have not been completely disclosed, and the role of both innate and the adaptive immunity is still under investigation.
M2 macrophage polarization, previously thought to be a specific feature of a progressing and fibrosing disease, has been related to the initial steps of granuloma formation both in animal and in-vitro models. The dysregulation of specific metabolic pathways and autophagy has been associated with disease activity and progression. T cells have been reported to be strongly influenced by a macrophage-driven microenvironment and more dangerous when acquiring hybrid phenotypes (e.g. Th17.1) or even becoming anergic, leading to disease chronicization. Locally released serum amyloid A was suggested to induce a more pro-inflammatory Th17 transcription program. The possible role of in-situ humoral immunity and bone marrow-derived mesenchymal stromal cells has also been highlighted.
Evidence points at microenvironment and cell functional features rather than cell polarization or differentiation as determinants of pathogenesis. In terms of therapeutic implications, future advances will rely on molecular disease profiling, aiming at personalized and combined therapeutic approaches.
结节病肉芽肿形成和疾病进展的免疫决定因素尚未完全揭示，先天免疫和适应性免疫的作用仍在研究中。
M2 巨噬细胞极化，以前被认为是进展性和纤维化疾病的一个特定特征，在动物和体外模型中均与肉芽肿形成的初始步骤有关。特定代谢途径和自噬的失调与疾病活动和进展有关。据报道，T 细胞受到巨噬细胞驱动的微环境的强烈影响，当获得混合表型（例如 Th17.1）甚至变得无反应时，更具危险性，导致疾病慢性化。局部释放的血清淀粉样蛋白 A 被认为可诱导更具炎症性的 Th17 转录程序。原位体液免疫和骨髓来源的间充质基质细胞的可能作用也已被强调。
有证据表明，微环境和细胞功能特征而不是细胞极化或分化是发病机制的决定因素。就治疗意义而言，未来的进展将依赖于分子疾病分析，旨在实现个体化和联合治疗方法。
