IL-10 suppresses Th17 cells and promotes regulatory T cells in the CD4+ T cell population of rheumatoid arthritis patients

Heo, Yu-Jung; Joo, Young-Bin; Oh, Hye-Jwa; Park, Mi-Kyung; Heo, Yang-Mi; Cho, Mi‐La; Kwok, Seung‐Ki; Ju, Ji-hyun; Park, Kyung-Su; Cho, Seok Goo; Park, Sung-Hwan; Kim, Ho-Youn; Min, Jun‐Ki

doi:10.1016/j.imlet.2009.10.006

Cited by 124 publications

(95 citation statements)

References 20 publications

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“…It is important also to note that the immune pathways associated with regulation of IL-17 are complex. For example, in support of our findings, opposing functions of IL-10 and various IL-17-producing cell types have been reported in other disease models, including infections (34,35) and, importantly, arthritis (36,37). However, cells which produce both cytokines exist (32,38), and IL-10-producing regulatory T (Treg) cells have also been shown to aid in the production of Th17 cells at certain periods of development (39).…”

Section: Discussionsupporting

confidence: 82%

Interleukin-10 (IL-10) Inhibits Borrelia burgdorferi-Induced IL-17 Production and Attenuates IL-17-Mediated Lyme Arthritis

et al. 2013

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Previous studies have shown that cells and cytokines associated with interleukin-17 (IL-17)-driven inflammation are involved in the arthritic response to Borrelia burgdorferi infection. Here, we report that IL-17 is a contributing factor in the development of Lyme arthritis and show that its production and histopathological effects are regulated by interleukin-10 (IL-10). Spleen cells obtained from B. burgdorferi-infected, "arthritis-resistant" wild-type C57BL/6 mice produced low levels of IL-17 following stimulation with the spirochete. In contrast, spleen cells obtained from infected, IL-10-deficient C57BL/6 mice produced a significant amount of IL-17 following stimulation with B. burgdorferi. These mice developed significant arthritis, including erosion of the bones in the ankle joints. We further show that treatment with antibody to IL-17 partially inhibited the significant hind paw swelling and histopathological changes observed in B. burgdorferi-infected, IL-10-deficient mice. Taken together, these findings provide additional evidence of a role for IL-17 in Lyme arthritis and reveal an additional regulatory target of IL-10 following borrelial infection.

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Section: Discussionsupporting

confidence: 82%

Interleukin-10 (IL-10) Inhibits Borrelia burgdorferi-Induced IL-17 Production and Attenuates IL-17-Mediated Lyme Arthritis

et al. 2013

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“…It has been established that IL-10 suppresses the functions of macrophages and neutrophils [70,72] , inhibits the Th1 immune response [70,[73][74][75][76] , influences NF-kB synthesis [77] and causes expression of anti-inflammatory molecules, such as protease inhibitors [78] and IL-1 and TNFα antagonists [79] . The major function of IL-10 in induction of immune tolerance is its effect on the antigen presenting cells and particularly on the dendritic cells (DCs).…”

Section: Interleukin 10mentioning

confidence: 99%

“…Further on, IL-10 is directly engaged in the induction of immune tolerance by two types of T regulatory lymphocytes: Tregs and Tr1 [76] . IL-10 is one of the cytokines related to the generation of Tregs [73] which secretes IL-10 by itself and this process has been described both for "natural" FoxP3+ Tregs and for FoxP3+ Tregs generated after response to a specific antigen [70,73,80] . A specific feature of IL-10 and some other cytokines is that the producing cells are both the source and target of the cytokine effect and this predominantly affects the dendritic and T regulatory cells.…”

Section: Interleukin 10mentioning

confidence: 99%

“…The effect of IL-10 is mediated via its binding to its specific receptor (IL-10R) and subsequent interaction between JAK1 and STAT-3 [73,77] , a mechanism which is common for many other cytokines. Besides the antigenpresenting cells and particularly tolerogenic DCs, Tregs and Tr1, other immune cells secrete IL-10 and these include T and B lymphocytes, NK cells, neutrophils and macrophages [76,80] .…”

Section: Interleukin 10mentioning

confidence: 99%

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Secretion of immunoregulatory cytokines by mesenchymal stem cells

Kyurkchiev

Bochev

Ivanova‐Todorova

et al. 2014

WJSC

526

392

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According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells (MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system. © 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Mesenchymal stem cells; Immunomodulation; Cytokines; Chemokines; Dendritic cells Core tip: Autoimmune diseases affect approximately 5% of the human population, leading to serious disability and effective methods to treat these diseases are still not perfect. Mesenchymal stem cells (MSCs) are assumed to be promising agents, both for regenerative medicine and cell therapy for autoimmune disorders. Under the influence of some factors, mesenchymal stem cells secrete cytokines which induce suppression of the immune response. Studies on the secreted cytokines and the precise mechanisms involved in these suppressive mechanisms would create possibilities for efficient application of MSCs as a therapeutic means for treatment of autoimmune diseases.Kyurkchiev D, Bochev I, Ivanova-Todorova E, Mourdjeva M, REVIEWSubmit a

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“…4 cells produced significantly higher levels of IL-10 over the entire course of culture ( Figure 2D). As it was shown that IL-10 could suppress Th17 cells and the production of IL-17, 40,41 we examined the levels of IL-17 in the culture supernatant of airway luminal and granuloma cell cultures. Indeed, airway luminal cells produced larger amounts of IL-17 than granuloma-derived cells (Table 2).…”

Section: Differential Pro-inflammatory and Anti-inflammatory Moleculementioning

confidence: 99%

Pulmonary Mycobacterial Granuloma

Shaler

Kugathasan

McCormick

et al. 2011

The American Journal of Pathology

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The granuloma, a hallmark of host defense against pulmonary mycobacterial infection, has long been believed to be an active type 1 immune environment. However, the mechanisms regarding why granuloma fails to eliminate mycobacteria even in immune-competent hosts, have remained largely unclear. By using a model of pulmonary Mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection, we have addressed this issue by comparing the immune responses within the airway luminal and granuloma compartments. We found that despite having a similar immune cellular profile to that in the airway lumen, the granuloma displayed severely suppressed type 1 immune cytokine but enhanced chemokine responses. Both antigen-presenting cells (APCs) and T cells in granuloma produced fewer type 1 immune molecules including tumor necrosis factor-␣ (TNF-␣), interferon-␥ (IFN-␥), and nitric oxide. As a result, the granuloma APCs developed a reduced capacity to phagocytose mycobacteria and to induce T-cell proliferation. To examine the molecular mechanisms, we compared the levels of immune suppressive cytokine IL-10 in the airway lumen and granuloma and found that both granuloma APCs and T cells produced much more IL-10. Thus, IL-10 deficiency restored type 1 immune activation within the granuloma while having a minimal effect within the airway lumen. Hence, our study provides the first experimental evidence that, contrary to the conventional belief, the BCG-induced lung granuloma represents a symbiotic host-microbe microenvironment characterized by suppressed type 1 immune activation.

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IL-10 suppresses Th17 cells and promotes regulatory T cells in the CD4+ T cell population of rheumatoid arthritis patients

Cited by 124 publications

References 20 publications

Interleukin-10 (IL-10) Inhibits Borrelia burgdorferi-Induced IL-17 Production and Attenuates IL-17-Mediated Lyme Arthritis

Interleukin-10 (IL-10) Inhibits Borrelia burgdorferi-Induced IL-17 Production and Attenuates IL-17-Mediated Lyme Arthritis

Secretion of immunoregulatory cytokines by mesenchymal stem cells

Pulmonary Mycobacterial Granuloma

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