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In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients
Published on: August 12, 2017
Interleukin-10 mediated immune regulation after stem cell transplantation: Mechanisms and implications for
1Bone Marrow Transplantation Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Interleukin-10 (IL-10) is a multi-faceted anti-inflammatory cytokine which plays an essential role in immune tolerance. Indeed, deficiency of IL-10 or its receptor results in aberrant immune responses that lead to immunopathology. Graft-versus-host disease (GVHD) is the limiting complication of allogeneic stem cell transplantation (SCT) and results from an imbalance in pathological versus regulatory immune networks. A number of immune cells exert their immunomodulatory role through secretion of IL-10 or induction of IL-10-secreting cells after SCT. Type-1 regulatory T cells (Tr1 cells) and FoxP3+ regulatory T cells (Tregs) are predominant sources of IL-10 after SCT and the critical role of this cytokine in preventing GVHD is now established. Recently, intriguing interactions among IL-10, immune cells, commensal microbes and host tissues in the gastrointestinal (GI) tract and other barrier surfaces have been uncovered. We now understand that IL-10 secretion is dynamically modulated by the availability of antigen, co-stimulatory signals, cytokines, commensal microbes and their metabolites in the microenvironment. In this review, we provide an overview of the control of IL-10 secretion and signaling after SCT and the therapeutic interventions, with a focus on Tr1 cells.
Interleukin-10 (IL-10) is a multi-faceted anti-inflammatory cytokine which plays an essential role in immune tolerance. Indeed, deficiency of IL-10 or its receptor results in aberrant immune responses that lead to immunopathology. Graft-versus-host disease (GVHD) is the limiting complication of allogeneic stem cell transplantation (SCT) and results from an imbalance in pathological versus regulatory immune networks. A number of immune cells exert their immunomodulatory role through secretion of IL-10 or induction of IL-10-secreting cells after SCT. Type-1 regulatory T cells (Tr1 cells) and FoxP3+ regulatory T cells (Tregs) are predominant sources of IL-10 after SCT and the critical role of this cytokine in preventing GVHD is now established. Recently, intriguing interactions among IL-10, immune cells, commensal microbes and host tissues in the gastrointestinal (GI) tract and other barrier surfaces have been uncovered. We now understand that IL-10 secretion is dynamically modulated by the availability of antigen, co-stimulatory signals, cytokines, commensal microbes and their metabolites in the microenvironment. In this review, we provide an overview of the control of IL-10 secretion and signaling after SCT and the therapeutic interventions, with a focus on Tr1 cells.
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