Division of Hematology and Blood & Marrow Transplant, Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA.
Int J Mol Sci. 2021 Feb 27;22(5):2385. doi: 10.3390/ijms22052385.
Allogeneic hematopoietic stem cell transplantation (HSCT) is most commonly a treatment for inborn defects of hematopoiesis or acute leukemias. Widespread use of HSCT, a potentially curative therapy, is hampered by onset of graft-versus-host disease (GVHD), classified as either acute or chronic GVHD. While the pathology of acute GVHD is better understood, factors driving GVHD at the cellular and molecular level are less clear. Mast cells are an arm of the immune system that are known for atopic disease. However, studies have demonstrated that they can play important roles in tissue homeostasis and wound healing, and mast cell dysregulation can lead to fibrotic disease. Interestingly, in chronic GVHD, aberrant wound healing mechanisms lead to pathological fibrosis, but the cellular etiology driving this is not well-understood, although some studies have implicated mast cells. Given this novel role, we here review the literature for studies of mast cell involvement in the context of chronic GVHD. While there are few publications on this topic, the papers excellently characterized a niche for mast cells in chronic GVHD. These findings may be extended to other fibrosing diseases in order to better target mast cells or their mediators for treatment of fibrotic disease.
同种异体造血干细胞移植(HSCT)最常用于治疗先天性造血缺陷或急性白血病。由于移植物抗宿主病(GVHD)的发生,HSCT 作为一种潜在的治愈疗法,其广泛应用受到了阻碍。GVHD 分为急性和慢性 GVHD。虽然急性 GVHD 的病理学研究更为透彻,但在细胞和分子水平上导致 GVHD 的因素尚不清楚。肥大细胞是免疫系统的一部分,其与特应性疾病有关。然而,研究表明它们在组织稳态和伤口愈合中可以发挥重要作用,肥大细胞失调会导致纤维化疾病。有趣的是,在慢性 GVHD 中,异常的伤口愈合机制导致病理性纤维化,但驱动这种机制的细胞病因尚不清楚,尽管一些研究暗示了肥大细胞的作用。鉴于这一新颖的作用,我们在此回顾了肥大细胞在慢性 GVHD 背景下的研究文献。虽然关于这个主题的出版物很少,但这些论文很好地描述了肥大细胞在慢性 GVHD 中的一个特定位置。这些发现可能会扩展到其他纤维化疾病,以便更好地针对肥大细胞或其介质进行纤维化疾病的治疗。