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IL-27 and IL-21 are...
IL-27 and IL-21 are associated with T cell IL-10 responses in human visceral leishmaniasis
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Ansari, NA (författare)
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Kumar, R (författare)
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Gautam, S (författare)
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- Nylen, S (författare)
- Karolinska Institutet
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Singh, OP (författare)
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Sundar, S (författare)
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Sacks, D (författare)
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(creator_code:org_t)
- 2011-04-01
- 2011
- Engelska.
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 186:7, s. 3977-3985
- Relaterad länk:
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http://www.jimmunol....
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http://kipublication...
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https://doi.org/10.4...
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Abstract
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- IL-10 is believed to underlie many of the immunologic defects in human visceral leishmaniasis (VL). We have identified CD4+CD25−Foxp3− T cells as the major source of IL-10 in the VL spleen. IL-27, a member of the IL-6/IL-12 cytokine family, has been shown to promote development of IL-10–producing T cells, in part by upregulating their production of autocrine IL-21. We investigated whether IL-27 and IL-21 are associated with human VL. IL-27 was elevated in VL plasma, and at pretreatment, spleen cells showed significantly elevated mRNA levels of both IL-27 subunits, IL-27p28 and EBI-3, as well as IL-21, compared with posttreatment biopsies. CD14+ spleen cells were the main source of IL-27 mRNA, whereas CD3+ T cells were the main source of IL-21. IL-27 mRNA could be strongly upregulated in normal donor macrophages with IFN-γ and IL-1β, conditions consistent with those in the VL spleen. Last, a whole-blood assay revealed that most VL patients could produce Ag-specific IFN-γ and IL-10 and that the IL-10 could be augmented with recombinant human IL-21. Thus, proinflammatory cytokines acting on macrophages in the VL spleen have the potential to upregulate IL-27, which in turn can induce IL-21 to expand IL-10–producing T cells as a mechanism of feedback control.
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