Expression of IL‐1Rrp2 by human myelomonocytic cells is unique to DCs and facilitates DC maturation by IL‐1F8 and IL‐1F9

Mutamba, Shilla; Allison, Asher; Mahida, Yashwant R.; Barrow, Paul; Foster, Neil

doi:10.1002/eji.201142035

Cited by 92 publications

(89 citation statements)

References 32 publications

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“…We then studied whether, or not, IL-36 β altered expression of IL-36R in CD4+ lymphocytes and found that IL-36R expression plateaued when the cells were incubated with 100-200 ng/ml IL-36β. Human IL-36α-γ have been shown before to be effective at relatively low doses, when compared to murine homologues [12][13]. The current study is, therefore, consistent with the latter since culture of CD4+ cells with IL-1β at 500 ng/ml decreased IL-36R expression, when compared to expression at 100-200 ng/ml, which also indicates a negative feedback loop shown in a previous paper [12].…”

Section: Discussionsupporting

confidence: 91%

“…Lamina propria cells were isolated from mucosal samples using a previously described technique [9]. table 1and as previously reported [12][13] and PCR product obtained was also shown to be of correct size as that previously reported [12].…”

Section: Isolation Of Human Ileal Lamina Propria Cellsmentioning

confidence: 66%

“…In our studies all reagents were LPS tested and the IL-36R antibody used was monoclonal, unlike the polyclonal antibody used in the aforementioned study. We also used the same PCR probe we successfully reported on before [12][13] and visualised the PCR product, using an agarose gel, which was found to be the correct size for IL-36R (data not shown). Our data shows differences in the expression pattern of IL-36R in different lymphocytes, with CD4+ lymphocytes (and to a lesser extent B lymphocytes) containing large cytoplasmic stores of the receptor, whereas in CD8+ lymphocytes most of the IL-36R…”

Section: Discussionmentioning

confidence: 99%

“…Classic IL-1 cytokines are known to indirectly induce T cell proliferation by enhancing APC maturation and survival [15][16] and we have recently shown that this is also the case for IL-36β and IL-36γ-stimulated human monocyte derived dendritic cells (MDDCs) [12]. Few studies have reported the direct effect of classic IL-1 cytokines on lymphocyte proliferation.…”

Section: Discussionmentioning

confidence: 99%

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IL-36 receptor is expressed by human blood and intestinal T lymphocytes and is dose–dependently activated via IL-36β and induces CD4+ lymphocyte proliferation

et al. 2016

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We show that IL-36R is expressed by T (CD4+ and CD8+) and B (CD19+) lymphocytes in human blood and also by CD4+ T lymphocytes in the intestinal lamina propria. IL-36R protein was mostly stored in the cytoplasm of CD4 lymphocytes and B cells, during steady andthe greatest expression of IL-36R mRNA was measured in CD4+ (T helper) lymphocytesIL-36 β, which functions via IL-36R induced rapid and significant (P <0.05) proliferation of CD4+ lymphocytes, within 48h. IL-36R expression was also maintained on the surface of circulating CD4+ lymphocytes which enter the intestinal lamina propria.In conclusion our study is the first to show that (1) all human blood lymphocytes express IL-36R; (2) IL-36R expression is maintained by circulating CD4+ lymphocytes which enter the intestinal lamina propria and (3) IL-36R/IL-36 β induces rapid CD4 lymphocyte proliferation. The possible significance of these results in the context of human disease is discussed.3

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Section: Discussionsupporting

confidence: 91%

Section: Isolation Of Human Ileal Lamina Propria Cellsmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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IL-36 receptor is expressed by human blood and intestinal T lymphocytes and is dose–dependently activated via IL-36β and induces CD4+ lymphocyte proliferation

et al. 2016

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“…IL-36 cytokines are new members of the IL-1 family that comprise three agonists, IL-36a, IL-36b, and IL-36g, that bind to the IL-36R and recruit the coreceptor IL-1R accessory protein, activating intracellular signals similar to those induced by other members of the IL-1 family. IL-36a, IL-36b, and IL-36g can stimulate the production of different cytokines by both human and mouse dendritic cells (DCs) (21,22). IL-36b can induce proliferation and IL-2 secretion in naive mouse T cells (Th0), and synergizes with IL-12 to stimulate Th1 responses (23).…”

mentioning

confidence: 99%

IL-36–Induced Toxicity in Neonatal Mice Involves TNF-α Production by Liver Myeloid Cells

Palomo

Mastelic-Gavillet

Woldt

et al. 2016

The Journal of Immunology

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Human and mouse neonates exhibit limited vaccine responses characterized by predominant Th2 and limited Th1 responses. Because IL-36 exerts a synergic adjuvant effect with IL-12, enhancing Th1 polarization in adult (AD) mice, we administered IL-36β to neonatal (1-wk old) and AD control mice at the time of immunization with tetanus toxoid adsorbed to aluminum hydroxide (TT/Alum). Unexpectedly, the combination of IL-36β with TT/Alum, which was well tolerated in AD mice, proved toxic and even lethal in neonates. This neonatal toxicity was associated with high Il36r mRNA expression in neonatal liver, resulting in increased cytokine production. Liver Il36r mRNA expression decreased with the termination of fetal liver hematopoiesis, and this decrease correlated with a complete protection from TT/Alum/IL-36β–induced mortality. The combination of IL-36β and TT/Alum induced the rapid production of TNF-α and IFN-γ by liver myeloid and lymphoid cells, respectively. These responses were less marked when IL-36β was used alone, with no adverse effect. The toxicity of IL-36β + TT/Alum was abrogated by the administration of a neutralizing anti–TNF-α Ab, confirming causality. In conclusion, liver myeloid cells in neonatal mice are an important source of proinflammatory cytokines that may lead to TNF-α–mediated toxicity and even lethality.

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The IL‐36 receptor pathway regulates Aspergillus fumigatus‐induced Th1 and Th17 responses

et al. 2012

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IL-1 drives Th responses, particularly Th17, in host defense. Sharing the same coreceptor, the IL-1 family member IL-36 exhibits properties similar to those of IL-1. In the present study, we investigated the role of IL-36 in Aspergillus fumigatus-induced human Th responses. We observed that different morphological forms of A. fumigatus variably increase steady-state mRNA of IL-36 subfamily members. IL-36α is not significantly induced by any morphological form of Aspergillus. Most strikingly, IL-36γ is significantly induced by live A. fumigatus conidia and heat-killed hyphae, whereas IL-36Ra (IL-36 receptor antagonist) is significantly induced by heat-killed conidia, hyphae, and live conidia. We also observed that IL-36γ expression is dependent on the dectin-1/Syk and TLR4 signaling pathway. In contrast, TLR2 and CR3 inhibit IL-36γ expression. IntroductionThe IL-1 family (IL-1F) consists of 11 members [1]. The in silico discovery of IL-1 family members IL-1F5, IL-1F6, IL-1F8, and IL-1F9 have recently been renamed IL-36 receptor antagonist (IL-36Ra), IL-36α, IL-36β, and IL-36γ, respectively. Presently, there is a paucity of data on the biological properties and functional roles of the IL-36 subfamily in health and disease. The clasCorrespondence: Dr. Frank L. van de Veerdonk e-mail: f.veerdonk@aig.umcn.nl sic IL-1 family members IL-1α and IL-1β as well as IL-18 and IL-33 polarize Th responses [1]. However, little is known about the role of the IL-36 subfamily (IL-36α, IL-36β, and IL-36γ) and the IL-36Ra in antimicrobial host defense. Each member of the IL-36 subfamily binds to IL-1Rrp2 (now renamed IL-36 receptor, IL-36R) and recruits the co-receptor for signal transduction, IL-1RAcP [2,3]. The IL-36R is expressed on dendritic cells (DCs) [4,5] and T cells [5]. Stimulation of T cells by IL-36R ligands results in the induction of , and DCs primed with IL-36 ligands are inducers of Th1 cells. Although the synthetic TLR3 ligand polyI:C induces IL-36γ secretion [6], nothing is known about the innate pattern recognition pathways that induce IL-36R ligands in the antimicrobial host defense.www.eji-journal.eu Eur. J. Immunol. 2013. 43: 416-426 Immunity to infection 417The opportunistic fungus Aspergillus fumigatus is ubiquitous; Aspergillus spores are inhaled daily by humans. Inhaled Aspergillus spores (conidia) are efficiently cleared in healthy individuals [7]. However, in immunocompromised persons, or in patients with preexisting lung injury, Aspergillus conidia germinate resulting in invasive infections associated with high mortality [8]. Th responses are important in the host defense against invasive aspergillosis [9], and the major known cytokine pathways that are involved in the induction of Th1 and Th17 responses are IL-12/IL-18 and IL-1/IL-23, respectively [9,10]. Next to the induction of the specific Th-axis, there is also interplay between these cytokine pathways. IFN-γ-induced IL-18 binding protein was found to downregulate the Th17 response [11], and in several cases the induction of Th17 or IL-17 produc...

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Expression of IL‐1Rrp2 by human myelomonocytic cells is unique to DCs and facilitates DC maturation by IL‐1F8 and IL‐1F9

Cited by 92 publications

References 32 publications

IL-36 receptor is expressed by human blood and intestinal T lymphocytes and is dose–dependently activated via IL-36β and induces CD4+ lymphocyte proliferation

IL-36 receptor is expressed by human blood and intestinal T lymphocytes and is dose–dependently activated via IL-36β and induces CD4+ lymphocyte proliferation

IL-36–Induced Toxicity in Neonatal Mice Involves TNF-α Production by Liver Myeloid Cells

The IL‐36 receptor pathway regulates Aspergillus fumigatus‐induced Th1 and Th17 responses

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