RORγt+ Innate Lymphoid Cells Acquire a Proinflammatory Program upon Engagement of the Activating Receptor NKp44

Glatzer, Timor; Killig, Monica; Meisig, Johannes; Ommert, Isabelle; Luetke-Eversloh, Merlin V.; Babić, Marina; Paclik, Daniela; Blüthgen, Nils; Seidl, R; Seifarth, Claudia; Gröne, Jörn; Lenarz, Minoo; Stölzel, Katharina; Fugmann, Dominik; Porgador, Angel; Hauser, Anja E.; Karlas, Alexander; Romagnani, Chiara

doi:10.1016/j.immuni.2013.05.013

Cited by 173 publications

(193 citation statements)

References 32 publications

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“…Some evidences, however, indicate that the engagement of NKp44 in ILC3 may induce TNF-α production and synergize with IL-1, IL-7, and IL-23 to induce secretion of IL-22 (a cytokine typically produced by ILC3s). 62 In a recent study, the transcriptome analysis of NKp44-stimulated ILCs revealed a “genome wide regulating effect”. 62 This finding is in line with our present proteomic study showing that NK cell stimulation both via mAb-mediated NKp44 cross-linking and by plastic-bound NID1 could induce significant changes in a relevant number of proteins.…”

Section: Discussionmentioning

confidence: 99%

“…62 In a recent study, the transcriptome analysis of NKp44-stimulated ILCs revealed a “genome wide regulating effect”. 62 This finding is in line with our present proteomic study showing that NK cell stimulation both via mAb-mediated NKp44 cross-linking and by plastic-bound NID1 could induce significant changes in a relevant number of proteins. Consistent with the multiple ligand specificities of NKp44 and its ability to mediate different functional responses, NKp44 cross-linking and NID1-induced stimulation resulted in protein changes that were only partially overlapping.…”

Section: Discussionmentioning

confidence: 99%

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Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

et al. 2018

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The release of soluble ligands of activating Natural Killer (NK) cell receptors may represent a regulatory mechanism of NK cell function both in physiologic and in pathologic conditions. Here, we identified the extracellular matrix protein Nidogen-1 (NID1) as a ligand of NKp44, an important activating receptor expressed by activated NK cells. When released as soluble molecule, NID1 regulates NK cell function by modulating NKp44-induced IFN-γ production or cytotoxicity. In particular, it also modulates IFN-γ production induced by Platelet-Derived Growth Factor (PDGF)-DD following NKp44 engagement. We also show that NID1 may be present at the cell surface. In this form or when bound to a solid support (bNID1), NID1 fails to induce NK cell cytotoxicity or cytokine release. However, analysis by mass spectrometry revealed that exposure to bNID1 can induce in human NK cells relevant changes in the proteomic profiles suggesting an effect on different biological processes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

et al. 2018

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“…NKp46 + ILC3 are characterized by subset‐restricted expression of multiple genes required for their development and maturation, such as Il12rb2 , Tbx21 and Notch1 ,51, 61 and are defined by expression of eponymous NK cell‐associated receptors. Recent evidence suggests that NKp46 expression may act as a novel pattern recognition molecule to facilitate responses to fungal pathogens,62 whereas engagement of NKp44 on human ILC3 results in pro‐inflammatory cytokine production 63. Although NCR + ILC3 are largely thought to be non‐cytotoxic cells, NKp46 + ILC3 express Gzmc – which encodes a murine granzyme molecule known to induce cell death 60, 64.…”

Section: Ilc3 Plasticity and Heterogeneitymentioning

confidence: 99%

Functional and phenotypic heterogeneity of group 3 innate lymphoid cells

2017

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SummaryGroup 3 innate lymphoid cells (ILC3), defined by expression of the transcription factor retinoid‐related orphan receptor γt, play key roles in the regulation of inflammation and immunity in the gastrointestinal tract and associated lymphoid tissues. ILC3 consist largely of two major subsets, NCR + ILC3 and LTi‐like ILC3, but also demonstrate significant plasticity and heterogeneity. Recent advances have begun to dissect the relationship between ILC3 subsets and to define distinct functional states within the intestinal tissue microenvironment. In this review we discuss the ever‐expanding roles of ILC3 in the context of intestinal homeostasis, infection and inflammation – with a focus on comparing and contrasting the relative contributions of ILC3 subsets.

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“…NCR + ILC3 are cellular sources of the tissue protective cytokine IL‐22 4. Additionally, engagement of NKp44 triggers TNF release providing a pro‐inflammatory function for NCR + ILC3 26. The NCR − ILC3 secrete little IL‐22 but do produce IL‐17, similarly to the LTi‐like ILC3 in the mouse 25.…”

Section: Ilc Subsetsmentioning

confidence: 99%

Innate Lymphoid Cells in Graft-Versus-Host Disease

Kónya

Mjösberg

2015

American Journal of Transplantation

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Innate lymphoid cells (ILC) are lymphocytes lacking rearranged antigen receptors such as those expressed by T and B cells. ILC are important effector and regulatory cells of the innate immune system, controlling lymphoid organogenesis, tissue inflammation, and homeostasis. The family of ILC consists of cytotoxic NK cells and the more recently described noncytotoxic group 1, 2, and 3 ILC. The classification of noncytotoxic ILC—in many aspects—mirrors that of T helper cells, which is based on the expression of master transcription factors and signature cytokines specific for each subset. The IL‐22 producing RORγt+ ILC3 subset was recently found to be critical in the prevention of intestinal graft‐versus‐host disease (GVHD) following allogeneic hematopoietic cell transplantation (HCT) via strengthening the intestinal mucosal barrier. In this review, we summarize the current view of the immunological functions of human noncytotoxic ILC subsets and discuss the potentially beneficial features of IL‐22 producing ILC3 in improving allo‐HCT efficacy by attenuating susceptibility to GVHD. In addition, we explore the possibility of other ILC subsets playing a role in GVHD.

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RORγt+ Innate Lymphoid Cells Acquire a Proinflammatory Program upon Engagement of the Activating Receptor NKp44

Cited by 173 publications

References 32 publications

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

Functional and phenotypic heterogeneity of group 3 innate lymphoid cells

Innate Lymphoid Cells in Graft-Versus-Host Disease

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