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Real-time quantitative PCR analysis of mouse skin samples

ABSTRACT: Development of chronic Graft Versus Host Disease (cGVHD) represents a major impediment in allogeneic hematopoietic stem cell transplantation (HSCT). This disorder has been shown to be associated with severe impairment of B-cell homeostasis, regulatory B-cell function and distribution. Conversely, the presence of bone marrow and circulating hematogones has been correlated with reduced GVHD risks. We herein raised the question whether B-cell progenitors that upon activation with the TLR-9 agonist CpG (CpG-proBs) provide protection in various models of autoimmune diseases, could as well reduce disease in a sclerodermatous model of cGVHD. We found that CpG-proBs, adoptively transferred during the initial phase of disease, reduced the diarrhea score and mostly prevented cutaneous fibrosis. Donor cells migrated to the draining lymph nodes and to the skin where they mainly differentiated into follicular B cells. CpG activation and IFN- expression were required for the protective effect, which resulted in reduced CD4+ T-cell-derived production of cytokines critically involved in cGVHD, such as TGF-, IL-13, IL-21. Adoptive transfer increased the ratio of follicular regulatory to helper T cells (TFh), which generated less IL-21 but more IL-10. Moreover, CpG-proBs privileged the accumulation of IL-10-expressing CD8+ T-cells, B-cells and dendritic cells in the skin. Collectively, these data support the notion that adoptively transferred CpG-proBs provide an efficient strategy for preventing sclerodermatous cGVHD either per se or as beneficial adjunct to the HSC graft.

ORGANISM(S): Mus musculus

PROVIDER: GSE182025 | GEO | 2021/10/21

REPOSITORIES: GEO

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