MRC National Institute for Medical Research, London
Science for Health
Understanding the production and role of interleukin 10
31 July 2009
Interleukin 10 (IL-10) is a cytokine with broad anti-inflammatory properties that inhibits macrophage and dendritic cell (DC) function. IL-10 limits the immune and inflammatory responses to pathogens and gut flora and prevents damage to the host but when dysregulated may result in chronic infection. IL-10 has recently been associated with regulatory CD4+ T cells; however IL-10 can be produced by many different types of T cells, including Th1 cells producing IFN-γ, important for activating macrophages to kill pathogens. This is ironic since IL-10 suppresses the production of IL-12 by macrophages and dendritic cells, IL-12 being the key factor inducing the differentiation of Th1 cells. IL-10 thus acts as a feedback loop to block over-exuberant Th1 immune responses and stop host damage.
Margarida Saraiva and Jillian Christensen, working with Anne O'Garra (pictured) in her lab in NIMR's Division of Immunoregulation, have shown that for Th1 cells to produce IL-10 they need to receive high level antigenic stimulus and also signalling from IL-12, both of which are probably representative of the environment of infected tissue. IL-10 production from Th1 cells is strictly under the control of the MAP kinase ERK - which also regulates the production of IL-10 by Th2 and Th17 cells, although each subset differentiates along a distinct pathway and produces a unique set of cytokines. The common pathway for IL-10 production by distinct Th1, Th2 and Th17 effectors strengthens the notion that IL-10 is not a subset cytokine but is produced by all different Th effector subsets to keep a lid on the immune response during infection.
Anne O'Garra said:
Our findings provide a mechanism whereby a Th1 cell responds to extrinsic signals, reflecting high level inflammation in the tissue, to tightly regulate the production of IL-10, so as to allow a protective response to eradicate a pathogen with minimal damage to the host, whilst preventing chronic infection. Moreover, our findings have important implications for the regulation of IL-10 production during an inflammatory Th1 response in infection and may be of relevance for the design of vaccines and for strategies in immunotherapy in infectious diseases.
Original article
The research findings are published in full in:
Margarida Saraiva, Jillian R. Christensen, Marc Veldhoen, Theresa L. Murphy, Kenneth M. Murphy and Anne O´Garra (2009)
Interleukin-10 production by Th1 cells requires interleukin-12-induced STAT4 transcription factor and ERK MAP kinase activation by high antigen dose
Immunity, epub ahead of print. Publisher abstract
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