Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA.
Cell. 2024 Jul 11;187(14):3506-3530. doi: 10.1016/j.cell.2024.05.015.
Fibrotic interstitial lung diseases (fILDs) have poor survival rates and lack effective therapies. Despite evidence for immune mechanisms in lung fibrosis, immunotherapies have been unsuccessful for major types of fILD. Here, we review immunological mechanisms in lung fibrosis that have the potential to impact clinical practice. We first examine innate immunity, which is broadly involved across fILD subtypes. We illustrate how innate immunity in fILD involves a complex interplay of multiple cell subpopulations and molecular pathways. We then review the growing evidence for adaptive immunity in lung fibrosis to provoke a re-examination of its role in clinical fILD. We close with future directions to address key knowledge gaps in fILD pathobiology: (1) longitudinal studies emphasizing early-stage clinical disease, (2) immune mechanisms of acute exacerbations, and (3) next-generation immunophenotyping integrating spatial, genetic, and single-cell approaches. Advances in these areas are essential for the future of precision medicine and immunotherapy in fILD.
纤维化性间质性肺疾病(fILD)的生存率较差,且缺乏有效的治疗方法。尽管肺纤维化存在免疫机制的证据,但免疫疗法在主要类型的 fILD 中均未取得成功。在这里,我们综述了肺纤维化中具有潜在临床影响的免疫机制。我们首先研究了广泛存在于各种 fILD 亚型中的固有免疫。我们说明了固有免疫在 fILD 中的作用涉及多种细胞亚群和分子途径的复杂相互作用。然后,我们回顾了适应性免疫在肺纤维化中的作用的不断增加的证据,以重新审视其在临床 fILD 中的作用。最后,我们提出了未来的研究方向,以解决 fILD 病理生物学中的关键知识空白:(1)强调临床疾病早期阶段的纵向研究,(2)急性加重的免疫机制,以及(3)整合空间、遗传和单细胞方法的下一代免疫表型。这些领域的进展对于 fILD 的精准医学和免疫疗法的未来至关重要。
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