Expression of CXCR4 on T-cell subsets and Plasma IL-17 Concentrations in Patients with Aplastic Anaemia

Abstract

Acquired aplastic anaemia (AA) is caused by T-cells migrating to and attacking bone marrow (BM) in response to chemokines (e.g., CXCR4). We investigated CXCR4 expressions on circulating T-cell subsets, plasma IL-17A concentrations, and their correlations with AA manifestations. We enrolled 71 patients with acquired AA (36 severe AA cases [SAA] and 35 non-severe AA cases [NSAA]) and 42 healthy volunteers. We used flow cytometry and ELISA to measure circulating CD4+ and CD8+ T-cells, their CXCR4 expressions, and plasma IL-17A concentrations. Compared to the healthy controls, SAA patients had fewer peripheral CD4+ T-cells, more CD8+ T-cells, and a significantly decreased CD4+/CD8+ ratio which was positively correlated with AA manifestations. Patients with SAA or NSAA had higher proportions of CD4+CXCR4+ and CD8+CXCR4+ T-cells, which were negatively correlated with haemoglobin concentrations and absolute neutrophil counts. Patients with SAA or NSAA had higher plasma IL-17A concentrations, which were negatively correlated with AA manifestations and the CD4+/CD8+ ratio. IL-17A concentrations showed a very week correlation with CD4+CXCR4+ T-cells frequencies, and no correlation with CD8+CXCR4+ T-cells frequencies. Aberrant CXCR4 expression may allow circulating T-cells, especially CD8+ T-cells, to infiltrate BM during AA progression. Elevated IL-17A concentrations may contribute to AA progression outside of the CXCR4-SDF-1α axis.

Small Paroxysmal Nocturnal Hemoglobinuria Clones in Autoimmune Hemolytic Anemia: Clinical Implications and Different Cytokine Patterns in Positive and Negative Patients

“…The former is a classic T-helper 1 cytokine involved in the autoimmune attack against bone marrow precursors typical of aplastic anemia (3) and reported elevated also in AIHA. Likewise, IL-17, a cytokine known to amplify the proinflammatory and autoimmune response, has been reported elevated in the same settings (17)(18)(19). In our study, PNH positive AIHA showed a Th1 profile more similar to hemolytic PNH than to "classic" (PNH negative) AIHA, suggesting that these small clones might mitigate Th1 response.…”

CXCR4, but not CXCR3, drives CD8+ T‐cell entry into and migration through the murine bone marrow

“…The CXCL12‐CXCR4 axis is not only important for homeostatic regulation of BM CD8 + T cells, but has also been implicated in the migration of pathogenic T cells to the BM. In aplastic anemia (AA), a disease characterized by T‐cell mediated destruction of the BM, CXCR4 is highly expressed on BM‐infiltrating CD4 + and CD8 + T cells in both mouse models and patients . In fact, symptoms of AA can be attenuated with pharmacological agents that block CXCR4 expression .…”

Differential mast cell phenotypes in benign versus cancer tissues and prostate cancer oncologic outcomes

“…We further found differential expression of inflammatory pathway‐related genes, such as CXCR4 , on tumor‐infiltrating mast cells. CXCR4 is a chemokine receptor for CXCL12 that is expressed by inflammatory cells including T cells, macrophages, and mast cells, and has been shown to play a role in mast cell recruitment [25,32,33]. The CXCL12–CXCR4 pathway in mast cells has been causally implicated in several cancers, including UV‐induced skin cancer, glioblastoma, and prostate cancer [34–36].…”