免疫学
移植物抗宿主病
造血干细胞移植
发病机制
促炎细胞因子
巨噬细胞
川地163
造血
巨噬细胞极化
移植
医学
生物
炎症
干细胞
疾病
病理
生物化学
遗传学
体外
外科
作者
Johanna Strobl,Laura Marie Gail,L. Krecu,Syra Madad,Lisa Kleißl,Luisa Unterluggauer,Anna Redl,Kveta Brazdilova,Simona Saluzzo,Philipp Wohlfarth,Hanna A. Knaus,Margit Mitterbauer,Werner Rabitsch,Muzlifah Haniffa,Georg Stary
摘要
Graft-versus-host disease (GvHD) is a major life-threatening complication of allogeneic haematopoietic stem cell transplantation (HSCT), limiting the broad application of HSCT for haematological malignancies. Cutaneous GvHD is described as a post-transplant inflammatory reaction by skin-infiltrating donor T cells and remaining recipient tissue-resident memory T cells. Despite the major influence of lymphocytes on GvHD pathogenesis, the complex role of mononuclear phagocytes (MNPs) in tissues affected by GvHD is increasingly appreciated.To characterize the identity, origin and functions of MNPs in patients with acute cutaneous GvHD.Using single-cell RNA sequencing and multiplex tissue immunofluorescence, we identified an increased abundance of MNPs in skin and blood from 36 patients with acute cutaneous GvHD. In cases of sex-mismatched transplantation, we used expression of X-linked genes to detect rapid tissue adaptation of newly recruited donor MNPs resulting in similar transcriptional states of host- and donor-derived macrophages within GvHD skin lesions.We showed that cutaneous GvHD lesions harbour expanded CD163+ tissue-resident macrophage populations with anti-inflammatory and tissue-remodelling properties including interleukin-10 cytokine production. Cell-cell interaction analyses revealed putative signalling to strengthen regulatory T-cell responses. Notably, macrophage polarization in chronic cutaneous GvHD types was proinflammatory and drastically differed from acute GvHD, supporting the notion of distinct cellular players in different clinical GvHD subtypes.Overall, our data reveal a surprisingly dynamic role of MNPs after HSCT. Specific and time-resolved targeting to repolarize this cell subset may present a promising therapeutic strategy in combatting GvHD skin inflammation.
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