Peripheral PDGFRα+gp38+ mesenchymal cells support the differentiation of fetal liver–derived ILC2

Summary In recent years, innate lymphoid cells (ILCs) have emerged as key mediators of protection and repair of mucosal surfaces during infection. The lung, a dynamic mucosal tissue that is exposed to a plethora of microbes, is a playground for respiratory infection‐causing pathogens which are not only a major cause of fatalities worldwide, but are also associated with comorbidities and decreased quality of life. The lung provides a rich microenvironment to study ILCs in the context of innate protection mechanisms within the airways, unraveling their distinct functions not only in health but also in disease. In this review, we discuss how pulmonary ILCs play a role in protection against viral, parasitic, bacterial, and fungal challenge, along with the mechanisms underlying this ILC‐mediated immunity.

Section: Ilcs In the Lungmentioning

confidence: 90%

Innate lymphoid cells in lung infection and immunity

Stehle

Hernandez

Romagnani

2018

“…Human ILC2s are capable of producing IL‐4, IL‐5, IL‐6, IL‐8, IL‐9, GM‐CSF, and amphiregulin in response to IL‐2 + IL‐33 . Moreover, a recent study showed that mouse ILC2s in the mesentery of the fetus and newborn are unable to respond to IL‐33 without co‐stimulatory cytokines while ILC2s in adult mesentery respond to IL‐33 alone …”

Section: Activating Cytokines (Il‐33 and Il‐25)mentioning

confidence: 99%

The group 2 innate lymphoid cell (ILC2) regulatory network and its underlying mechanisms

Kabata

Moro

Koyasu

2018

Self Cite

215

183

Summary Group 2 innate lymphoid cells (ILC2s) play critical roles in the induction of type 2 inflammation, response to parasite infection, metabolic homeostasis, and tissue repair. These multifunctional roles of ILC2s are tightly controlled by complex regulatory systems in the local microenvironment, the disruption of which may cause various health problems. This review summarizes up‐to‐date knowledge regarding positive and negative regulators for ILC2s based on their function and signaling pathways, including activating cytokines (IL‐33, IL‐25; MAPK, NF‐κB pathways), co‐stimulatory cytokines (IL‐2, IL‐7, IL‐9, TSLP; STAT5, IL‐4; STAT6, TNF superfamily; MAPK, NF‐κB pathways), suppressive cytokines (type1 IFNs, IFN‐γ, IL‐27; STAT1, IL‐10, TGF‐β), transdifferentiation cytokines (IL‐12; STAT4, IL‐1β, IL‐18), lipid mediators (LTC4, LTD4, LTE4, PGD2; Ca2+‐NFAT pathways, PGE2, PGI2; AC/cAMP/PKA pathways, LXA4, LTB4), neuropeptides (NMU; Ca2+‐NFAT, MAPK pathways, VIP, CGRP, catecholamine, acetylcholine), sex hormones (androgen, estrogen), nutrients (butyrate; HDAC inhibitors, vitamins), and cell‐to‐cell interactions (ICOSL‐ICOS; STAT5, B7‐H6‐NKp30, E‐cadherin‐KLRG1). This comprehensive review affords a better understanding of the regulatory network system for ILC2s, providing impetus to develop new treatment strategies for ILC2‐related health problems.

“…In addition, a Lin − CD127 + ILC that expresses chemoattractant receptor homologous molecule expressed on Th2 lymphocytes (CRTH2) and natural killer cell marker CD161 populates the fetal gut and responds to IL‐25 and IL‐33 to produce type 2 cytokines . In mice, fetal gut Arginase‐1 + Id2 + ILC precursors have the capacity to differentiate into ILC1s, ILC2s, and ILC3s, and the ILC2 development is supported by mesenteric platelet‐derived growth factor receptor α (PDGFRα) + glycoprotein‐38 (gp38) + mesenchymal cells . In a recent study, Koning and colleagues identified a Lin − CD7 + CD127 − CD45RO + CD56 + population by mass cytometry in human fetal intestine could develop into CD45RA + NK cells and CD127 + RORγt + ILC3s .…”

Section: Tissue‐related Control Of Ilc Maturation and Functionalitymentioning

confidence: 99%

Thinking differently about ILCs—Not just tissue resident and not just the same as CD4⁺ T‐cell effectors

Huang

Mao

Germain

2018

Innate lymphoid cells (ILCs) resemble adaptive T lymphocytes based on transcription factor expression, cytokine production, and their presumptive roles in immunity, but are activated for effector function through cytokine signaling and not antigen-specific receptors. The prevailing view is that ILCs adapt to specific microenvironments during development and operate as tissue-resident cells in co-operation with antigen-specific T cells to provide host protection and contribute to tissue maintenance. In particular, conventional models equate the activity of different ILC subsets with CD4+ effector T-cell types based on corresponding transcription factor expression and a potential for comparable cytokine production. Based on recent data from our laboratory, we suggest that these views on tissue residence and parallel functioning to CD4+ T cells are too restrictive. Our findings show that ILC2s can be mobilized from the gut under inflammatory conditions and contribute to distal immunity in the lungs during infection, whereas gut-resident ILC3s operate in a quite distinct manner from Th17 CD4+ effector cells in responding to commensal microbes, with important implications for control of metabolic homeostasis. In this review, we discuss the recent advances leading to these revised views of ILC inter-organ trafficking and the distinct and complementary function of ILCs with respect to adaptive T cells in establishing and maintaining a physiologic host environment.