Human IL‐19 regulates immunity through auto‐induction of IL‐19 and production of IL‐10

Jordan, William J.; Eskdale, Joyce; Boniotto, Michele; Lennon, Greig P.; Peat, Jon; Campbell, John; Gallagher, Grant

doi:10.1002/eji.200425317

Cited by 80 publications

(77 citation statements)

References 38 publications

(43 reference statements)

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“…[62][63][64] IL-19 also alters the induction of human mDC, such that they display elevated IL-10 secretion with no effect on IL-12. 65 We show here that IFN-l1 upregulated mDC IL-12 secretion with a corresponding reduction of IL-10 secretion and consistently diminished the Th2 response in several experimental systems. This result complements our previously observed effect of IL-19 on mDC, where IL-10 was elevated and IL-12p70 was unaffected.…”

Section: Discussionmentioning

confidence: 50%

Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

et al. 2007

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Interferon lambda-1 (IFN-l1/IL-29) is a member of the Type-III interferon family, which contains three ligands: IFN-l1, 2 and 3. These three ligands use the same unique heterodimeric receptor composed of CRF2-12 (IFN-l-R1/IL-28Ra) and CRF2-4 (IL10-R-b) chains. Like their close relatives, the Type-I interferons, IFN-l1, 2 and 3, promote the phosphorylation of STAT1 and STAT2, induce the ISRE3 complex, elevate OAS and MxA expression and exhibit antiviral activity in vitro. Their use of the IL10-R-b chain and their ability to phosphorylate STAT3, STAT4 and STAT5 suggested that they may also exhibit immunomodulatory activity; their antiviral action led us to hypothesize that this activity might be directed toward the Th1/Th2 system. Here, we have demonstrated that IFN-l1 altered the activity of Th cells in three separate experimental systems: (i) mitogen stimulation, (ii) mixed-lymphocyte reaction (MLR) and (iii) stimulation of naive T cells by monocyte-derived dendritic cells (mDC). In Con-A stimulation assays, the inclusion of IFN-l1 consistently led to markedly diminished levels of secreted interleukin (IL-13) with occasional coincident, modest elevation of secreted IFN-g. IL-13 secretion was 100-fold more sensitive to IFN-l1 than was IFN-g secretion. These observations were also made in the allogeneic two-way MLR. IFN-l1 was able to alter cytokine-mediated Th biasing and when naive T cells were exposed to allogeneic mDC that had been matured in the presence of IFN-l1, secreted IL-13 was again markedly and consistently reduced, whereas secreted IFN-g was largely unaltered. These functions were independent of IL-10. Our data support a hitherto unsuspected role for IFN-l1 in modulating the development of Th1 and Th2 cells, with an apparent emphasis on the diminution of IL-13 secretion.

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Section: Discussionmentioning

confidence: 50%

Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

et al. 2007

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“…PBMC and supernatants were harvested from donors as described for Figure 1. Secreted IFN-g protein levels were measured by ELISA as previously described by Jordan et al 32 No IFN-g protein levels were detected before 24 h. Q-RTPCR for IFN-g mRNA was conducted as described for the chemokines, using the following primers: IFN-g (NM_700219) Fwd-CCA.ACG.CAA.AGC.AAT.ACA.TGA, Rev-CGC.TTC.CCT.GTT.TTA.GCT.GC. 27 From these data, we can infer that donors can be classified generally as early or late responders to IFN-l1 with respect to MIG, IP-10 and I-TAC expression.…”

mentioning

confidence: 99%

Interferon lambda-1 (IFN-λ1/IL-29) induces ELR− CXC chemokine mRNA in human peripheral blood mononuclear cells, in an IFN-γ-independent manner

et al. 2007

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Interferon lambda-1 (IFN-l1), the prototype Type-III interferon, has antiviral functions similar to those of the Type-I interferons, IFN-a and IFN-b. However, IFN-l1 is capable of signaling through almost all STAT molecules and so it is possible that it may have novel immunoregulatory functions in addition to antiviral ones. From a range of chemokines tested, IFN-l1 elevated mRNA levels of only 'Monokine induced by IFN-gamma' (MIG/CXCL9), 'IFN-gamma inducible protein-10' (IP-10/CXCL10) and 'IFN-gamma inducible T-cell a chemoattractant' (I-TAC/CXCL11) from human peripheral blood mononuclear cells. As their names suggest, these chemokines are also induced by IFN-g, the only member of the Type-II interferon family. This action of IFN-l1 did not depend on intermediate induction of IFN-g and is therefore, likely to be independent of IFN-g. Further, our results suggest that donors responded to IFN-l1 stimulation either 'early' or 'late'. Overall the action of IFN-l1 was similar to that previously reported for IFN-g and may invite more detailed investigation of the role of IFN-l1 at the innate/adaptive interface.

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“…A role of IL-19 in skin inflammation is more in line with the expression pattern of its receptor complex, which is expressed by keratinocytes [62][63][64]. In human psoriatic lesions, IL-19 is expressed in epidermis above the dermal papillae, as shown in the first report to demonstrate the presence of this cytokine in keratinocytes [67].…”

Section: Il-19mentioning

confidence: 99%

“…For instance, monocytes do not seem to express IL-20R1 [9,62], and yet IL-19 has been reported to stimulate IL-6 and TNF release from monocytes, resulting in TNF-a-mediated cell apoptosis [61], or to regulate its own production and production of IL-10 [63]. Similarly, IL-19 was reported to promote the maturation of T cells towards Th2 polarization in mouse and human models [64,65].…”

Section: Il-19mentioning

confidence: 99%

Structure and function of interleukin-22 and other members of the interleukin-10 family

Trivella

Ferreira-Junior

Dumoutier

et al. 2010

Cell. Mol. Life Sci.

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The IL-10 family of cytokines is comprised of IL-10, . The IL-10 family members bind to shared class II cytokine receptor chains that associate in various combinations in heterodimeric complexes. Upon interleukin/receptor complex formation, these proteins switch on the Jak/STAT pathway and elicit pleiotropic biological responses whose variety sharply contrasts with their structural similarities. IL-10 family members are involved in several human diseases and health conditions and hence their structural analyses may provide valuable information to design specific therapeutic strategies. In this review, we describe the human interleukin-10 family of cytokines, focusing on their structures and functions, with particular attention given to IL-22 and IL-10. We report on the recently published structures of IL-10 cytokine family members and their complexes with cognate transmembrane and soluble receptors as well as on interleukin physiology and physiopathology.

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Human IL‐19 regulates immunity through auto‐induction of IL‐19 and production of IL‐10

Cited by 80 publications

References 38 publications

Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

Interferon lambda-1 (IFN-λ1/IL-29) induces ELR− CXC chemokine mRNA in human peripheral blood mononuclear cells, in an IFN-γ-independent manner

Structure and function of interleukin-22 and other members of the interleukin-10 family

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