Donor and host B cell‐derived IL‐10 contributes to suppression of graft‐versus‐host disease |
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Authors: | Michael Weber Pamela Stein Steve Prüfer Berenice Rudolph Andreas Kreft Edgar Schmitt Tobias Bopp Axel Roers Hansjörg Schild Simon Fillatreau Markus P. Radsak |
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Affiliation: | 1. Institute of Immunology, Johannes Gutenberg‐University Medical Center, Mainz, Germany;2. Department of Dermatology, Johannes Gutenberg‐University Medical Center, Mainz, Germany;3. Institute of Pathology, Johannes Gutenberg‐University Medical Center, Mainz, Germany;4. Institute of Immunology, Carl Gustav Carus University, Dresden, Germany;5. Deutsches Rheuma‐Forschungszentrum, Leibniz Institute, Berlin, Germany;6. Third Department of Medicine, Johannes Gutenberg‐University Medical Center, Mainz, Germany |
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Abstract: | 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 CD5intCD1dintTIM‐1int 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. |
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Keywords: | B cells IL‐10 Graft‐versus‐host disease |
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