CXCL10: most consistent cGVHD biomarker?

Abstract

In this issue of Blood, Kariminia et al report that serum CXCL10 is the only consistent biomarker for chronic graft-versus-host disease (cGVHD) and is associated with low peripheral blood levels of CXCR3⁺ natural killer (NK) cells.

Possible involvement of CXCL9 and CXCL10 in cGVHD pathogenesis. Naive lymphocytes (T and NK) traffic to local lymph nodes, where they recognize recipient minor antigen (mAg) presented by antigen-presenting cells in the T-cell zone. In parallel, B cells are activated in the germinal center. Primed naive cells convert to mAg-specific effector cells and exit the lymph nodes. Upon CXCL9 and CXCL10 release by circulating monocytes, the activated lymphocytes acquire CXCR3 on their surface leading to their recruitment in the target tissues via a CXCL9/CXCL10 gradient and a decrease of their frequencies in the blood. CD4/CD8⁺ T cells and possibly NK cells recognize recipient mAg expressed on major histocompatibility complex (MHC) I and MHC II or a to-be-determined NK receptor expressed by the epithelium, respectively. Then, effectors will kill tissue targets, promoting local cytokine and chemokine production, and setting up a cycle of tissue destruction and further effector recruitment. Professional illustration by Patrick Lane, ScEYEnce Studios.