6533b7d4fe1ef96bd1261d4f
RESEARCH PRODUCT
Donor and host B cell-derived IL-10 contributes to suppression of graft-versus-host disease
Hansjörg SchildTobias BoppAndreas KreftPamela SteinAxel RoersEdgar SchmittMarc WeberSimon FillatreauMarkus P. RadsakBerenice M. RudolphSteve Prüfersubject
biologymedicine.medical_treatmentImmunologychemical and pharmacologic phenomenaSpleenmedicine.diseaseInterleukin 10surgical procedures operativemedicine.anatomical_structureGraft-versus-host diseaseCytokineimmune system diseasesCD1DImmunologybiology.proteinmedicineImmunology and AllergyCD5Mode of actionB celldescription
Graft-versus-host disease (GvHD) is a frequent life-threatening complication following allogeneic HSC transplantation (HSCT). IL-10 is a regulatory cytokine with important roles during GvHD, yet its relevant sources, and mode of action, remain incompletely defined in this disease. Using IL-10-deficient donor or host mice (BALB/c or C57BL/6, respectively) in a MHC-mismatched model for acute GvHD, we found a strongly aggravated course of the disease with increased mortality when either donor or host cells could not produce this cytokine. A lack of IL-10 resulted in increased allogeneic T-cell responses and enhanced activation of host DCs in spleen and MLNs. Remarkably, IL-10 was prominently produced by host- and donor-derived CD5(int) CD1d(int) TIM-1(int) B cells in this disease, and consistent with this, allogeneic HSCT resulted in exacerbated GvHD when mice lacking IL-10 expression in B cells were used as donor or host, compared with controls. Taken together, this study demonstrates that host and donor B cell-derived IL-10 provides a unique mechanism of suppression of acute GvHD, and suggests that DCs are the targets of this B cell-mediated suppressive effect. These findings open novel therapeutic possibilities based on the use of B cells to increase the feasibility of allogeneic HSCT.
year | journal | country | edition | language |
---|---|---|---|---|
2014-03-25 | European Journal of Immunology |