Circulating monocyte subsets in human chronic graft-versus-host disease

Abstract

Chronic graft-versus-host disease (cGVHD) is a major cause of late morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Monocytes/macrophages play a central role in inflammation, tissue repair, and fibrosis, which are the main clinical features of cGVHD. Here, we examined the expression levels of activation markers, chemokine receptors, and scavenger receptors for each circulating monocyte subset in 145 patients without disease recurrence at least 12 months after undergoing allogeneic HCT. There were no significant differences in the numbers and the proportions of each monocyte subset between patients without cGVHD and those with mild or moderate/severe cGVHD. Lower expression of CCR5 on classical monocytes, and higher expression of CD204 and lower expression of CXCR1 on non-classical monocytes were associated with joint, and lung cGVHD, respectively. These data showed that alterations of activation markers and chemokine and scavenger receptors in each circulating monocyte subset were associated with the development of organ-specific cGVHD. Alterations of surface markers in each circulating monocyte subset may be candidate biomarkers for cGVHD.

B regulatory cells and monocyte subpopulations in patients with chronic graft-vs-host disease

“…Classical monocytes were also found to be associated with a higher NIH global severity score and mouth cGVHD. In contrast, Konuma et al ( 37 ), who investigated circulating monocyte subsets in cGVHD patients, found no difference in the numbers and the proportions of circulating monocyte subsets. However, their study revealed that altered expressions of activation markers and chemokine and scavenger receptors on each monocyte subset were significantly associated with specific organ involvement of cGVHD.…”

Human Effectors of Acute and Chronic GVHD Overexpress CD83 and Predict Mortality

“…While CD83 expression on Tfh was unreported prior to our present work, Tfh orchestrate critical aspects of autoreactive B cell activation in chronic GVHD (15,33). Additionally, monocytes and related interferon-inducible genes are associated with end organ damage in chronic GVHD (34). Therefore, we investigated CD83 expression among circulating B cells, Tfh, and monocytes at time of chronic GVHD diagnosis, prior to the initiation of systemic glucocorticoid therapy.…”

The Biological and Clinical Relevance of G Protein-Coupled Receptors to the Outcomes of Hematopoietic Stem Cell Transplantation: A Systematized Review

“…The expression of CXCL9 [267,268,269,270,271], CXCL10 [265,266,269,270,272,273], and CXCL11 [270], as well as their common receptor, CXCR3 [269,270,271,272,273,274], correlated positively with cGvHD in humans. Some chemokine receptors (CCR1, 3, 6, 7, 9) [263,275,276,277] showed positive correlation, whereas the correlation with some others (CXCR5, CX3CR1) [278,279] was negative. The available evidence on CCR4 and CCR5 is conflicting.…”

“…However, in another study, CCR4 + CD4 + T cells were associated with lower cGvHD [280], although the authors did not specify the subset of CD4 + T cells in question. Similarly, lower CCR5 on monocytes could be associated with cGvHD in joints [279]. Considering the large variety of immune cells involved in cGvHD, chemokines are naturally expected to play different roles during its course.…”