Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: Jan. 13, 2025
Language: Английский
Nature reviews. Immunology, Journal Year: 2019, Volume and Issue: 19(10), P. 599 - 613
Published: July 26, 2019
Language: Английский
Citations
220
Cell Research, Journal Year: 2020, Volume and Issue: 30(6), P. 475 - 491
Published: May 6, 2020
Abstract The multifaceted organization of the immune system involves not only patrolling lymphocytes that constantly monitor antigen-presenting cells in secondary lymphoid organs but also establish permanent tissue-residency. integration respective tissue and adaption to organ milieu enable tissue-resident signaling circuits with parenchymal coordinate responses maintain homeostasis. Innate (ILCs) are innate have a similar functional diversity T including lineage-specifying transcription factors drive certain effector programs. Since their formal discovery 10 years ago, it has become clear ILCs present almost every strongly enriched at barrier surfaces, where they regulate immunity infection, chronic inflammation, maintenance. In this context, recent research identified as key orchestrating homeostasis through ability sustain bidirectional interactions epithelial cells, neurons, stromal adipocytes, many other cells. review, we provide comprehensive discussion studies define development heterogeneity ILC populations impact on adaptive immunity. Further, discuss emerging influence nervous system, circadian rhythm, developmental plasticity function. Uncovering control function will an integrated view how tissues synchronized relevance far beyond classical role discrimination between self/non-self host defense.
Language: Английский
Citations
154
Trends in Immunology, Journal Year: 2020, Volume and Issue: 41(10), P. 902 - 917
Published: Sept. 8, 2020
Recent progress in the characterization of innate lymphoid cells (ILCs) across various organs mice and humans has revealed distinct ILC phenotypes functionalities depending on their localization.Transcriptional profiling genetic engineering have identified tissue-specific functions ILC1 mice. In humans, definition is controversial poorly understood, which complicates comparison between organs.ILC2 display a relatively homogeneous phenotype different tissues humans. Tissue variations are restricted to receptors involved sensing environmental signals such as cytokines.ILC3 differ homing receptor expression patterns, antigen-presentation ability, cytokine responsiveness not only but also niches within tissues. Although function circulating immune cell compartment been studied detail for decades, limitations terms access yields from peripheral our understanding tissue-based immunity, particularly advances high-throughput protein analyses, transcriptional profiling, epigenetics partially overcome these obstacles. Innate predominantly tissue-resident, accumulating data indicate that they significant functions. We summarize current knowledge aiming clarify immunity anatomical locations. comprise non-T, non-B, A universal nomenclature proposed 2018 [1.Vivier E. et al.Innate cells: 10 years on.Cell. 2018; 174: 1054-1066Abstract Full Text PDF PubMed Scopus (346) Google Scholar] segregated ILCs into five subsets: natural killer (NK) cells, ILC1, ILC2, ILC3, tissue inducer (LTi, see Glossary), NK latter some tissues, demonstrate cytotoxic activity [2.Riggan L. al.True detective: unraveling group 1 lymphocyte heterogeneity.Trends Immunol. 2019; 40: 909-921Abstract (7) Scholar]. CD56dim lack interleukin (IL)-7 subunit α (IL-7R-α, known CD127), CD56bright express intermediate amounts, show high CD127 [3.Spits H. al.NK type partners host defense.Nat. 2016; 17: 758-764Crossref Scholar,4.Judge C.J. al.CD56 bright IL-7Rα negatively associates with HCV level, IL-7-induced impaired during HIV infections.J. Leukoc. Biol. 2017; 102: 171-184Crossref (6) However, although IL-7R-α, develop even absence IL-7 [5.Robinette M.L. al.IL-15 sustains IL-7R-independent ILC2 ILC3 development.Nat. Commun. 8: 14601Crossref (51) Scholar], development relies signaling through common γ-chain [6.Spits Di Santo J.P. The expanding family Regulators effectors remodeling.Nat. 2011; 12: 21-27Crossref (574) Moreover, antigen-specific receptors, share phenotypic functional characteristics CD4+ T helper (Th) where mirror Th1, Th2, Th17 [7.Colonna M. diversity, plasticity, unique immunity.Immunity. 48: 1104-1117Abstract (80) despite similarities, arise developmental pathways epigenetic programs, suggestive nonredundant roles [8.Shih H.Y. al.Developmental acquisition regulomes underlies functionality.Cell. 165: 1120-1133Abstract (138) Scholar, 9.Koues O.I. al.Distinct gene regulatory human versus adaptive cells.Cell. 1134-1146Abstract (78) 10.Ercolano G. shared cells.J. 2020; 108: 723-737Crossref (0) Similarly Th subsets, regulated by transcription factor (TF) T-bet produce interferon (IFN)-γ, whereas governed Gata-binding (GATA)-3 mainly secrete IL-5 IL-13. dependent retinoid-related orphan γt (RORγt) aryl hydrocarbon (AHR), release IL-17 IL-22 Scholar,11.Spits cells-a proposal uniform nomenclature.Nat. Rev. 2013; 13: 145-149Crossref LTi formation secondary (SLOs) embryogenesis, depend RORγt [12.Eberl al.An essential nuclear generation fetal cells.Nat. 2004; 5: 64-73Crossref (689) mostly reside mucosal linings, might play tissue-protective or inflammatory Parabiosis experiments demonstrated ILCs, tissue-resident [13.Gasteiger al.Tissue residency nonlymphoid organs.Science. 2015; 350: 981-985Crossref (327) under conditions, concept challenged other reports [14.Huang Y. al.S1P-dependent interorgan trafficking 2 supports defense.Science. 359: 114-119Crossref (134) From further mouse studies, it nonetheless becoming increasingly clearer pool residing given result waves adult life – phenomenon termed layered ontogeny [15.Schneider C. al.Tissue-resident differentiate situ perinatal priming.Immunity. 50: 1425-1438Abstract (39) Scholar,16.Oherle K. al.Insulin-like growth pulmonary niche promotes 3 newborn lungs.Immunity. 52: 275-294Abstract (4) Nevertheless, how differs remains obscure. origin technically challenging address, there evidence local can at least be replenished infiltration differentiation naïve so-called precursors (ILCP) [17.Lim A.I. al.Systemic provide substrate differentiation.Cell. 168: 1086-1100Abstract (170) Scholar,18.Nagasawa al.KLRG1 NKp46 discriminate subpopulations CD117+CRTH2− biased toward ILC3.J. Exp. Med. 216: 1762-1776Crossref Reflecting impact microenvironment function, recent studies profound signatures heterogeneity [19.Yudanin N.A. al.Spatial temporal mapping reveals elements specificity.Immunity. 505-519Abstract (28) [20.Gury-BenAri al.The spectrum landscape intestinal shaped microbiome.Cell. 166: 1231-1246Abstract (215) respectively. Accumulating suggests exert receive. this review we features discuss differences contribute profiles highlighting parallels Understanding impacted microenvironments important improving therapeutic strategies pathologies affect specific Numerous over past Lin−NK1.1+NKp46+ highly heterogeneous pattern cell-surface markers TFs environments do unravel excellently reviewed elsewhere instead focus reported ILC1. defined lymphocytes, migratory reported. CD62L+CCR7+ most prevalent subset blood (CD127+Lin−NK1.1+NKp46+T-bet+) [21.Dutton E.E. al.Peripheral lymph nodes contain resident populations.Sci. 4eaau8082Crossref (11) possibly representing an immature precursor more mature subsets liver, CD49a+CD49b− TF Eomes (Figure 1). These amounts IFN-γ, granzyme C, tumor necrosis ligand superfamily member (TNFSF10, TRAIL) target killing [22.Peng al.Liver-resident confer skin-contact inflammation.J. Clin. Invest. 123: 1444-1456Crossref (291) 23.Daussy al.T-bet instruct two lineages liver bone marrow.J. 2014; 211: 563-577Crossref (284) 24.Sojka D.K. thymic conventional splenic cells.elife. 3: e01659Crossref (283) 25.Robinette al.Transcriptional programs define molecular classes subsets.Nat. 16: 306-317Crossref (329) 26.Weizman O. El al.ILC1 early protection initial sites viral infection.Cell. 171: 795-808Abstract (122) 27.Gordon S.M. factors control key checkpoints maturation.Immunity. 2012; 36: 55-67Abstract (394) 28.Takeda al.TRAIL identifies liver.Blood. 2005; 105: 2082-2089Crossref (186) There discrepancies observed levels A/B/C intestine [23.Daussy Scholar,25.Robinette Scholar,26.Weizman Scholar,29.Klose C.S.N. al.Differentiation progenitor all helper-like lineages.Cell. 157: 340-356Abstract (588) cytolytic being [24.Sojka Of note, surface employed separate small intestine, identify ILC1/NK populations [25.Robinette Because overlapping functions, especially so far no clear distinction types. Single-cell RNA sequencing (scRNA-seq) lamina propria (siLP) presence four states, ILC1a–d characterized graded Tbx21 (encoding T-bet). Whereas ILC1a lowest Ifng, ILC1d highest Tbx21, Gzmb (granzyme B), Gzmc, suggesting degree specialization among Compared spleen siLP showed activated profile, perhaps because microbial environment modulates lead versatile responses states (ILC1a–d) Nfil3, required intraepithelial (ieILC1)/NK (NKp46+NK1.1+CD160+) well CD49b−Eomes− adipose Scholar,30.Fuchs A. al.Intraepithelial IL-12- IL-15-responsive IFN-γ-producing cells.Immunity. 38: 769-781Abstract (492) 31.Geiger T.L. al.Nfil3 crucial against pathogens.J. 1723-1731Crossref (158) 32.O'Sullivan T.E. al.Adipose-resident promote obesity-associated insulin resistance.Immunity. 45: 428-441Abstract skin, salivary glands, uterus Nfil3 Scholar,33.Cortez V.S. al.Salivary gland sevelop independently steady-state.J. 192: 4487-4491Crossref one could speculate progenitors and/or execute maturation program environment. This theory supported fact dramatically reduced Zfp683−/− (Zfp683 encodes Hobit) relative wild-type (WT) [26.Weizman Scholar,34.Mackay L.K. al.Hobit Blimp1 lymphocytes.Science. 352: 459-463Crossref (278) More fate-mapping will necessary account organ-specific origins features. Several including CD90, CD69, CD49a, Ly6C, CD103, CD61 were found differentially expressed Scholar,35.Cortez al.Transforming factor-β guides glands.Immunity. 44: 1127-1139Abstract Scholar,36.Park al.Toxoplasma gondii infection drives conversion ILC1-like cells.eLife. e47605Crossref (8) addition phenotypes, becomes complex upregulate TRAIL, decrease Eomes, upon transfer murine cytomegalovirus (MCMV)-infected mice, response proinflammatory cytokines vivo vitro Scholar,37.Bezman al.Molecular identity activation 1000-1008Crossref Scholar,38.Sheppard S. NKp46/NCR1 controls TRAIL ILC1s.Cell Rep. 22: 3385-3392Abstract (18) inhibitory CD200r1 represent stable marker several tissue, spleen, peritoneal cavity cell-related reported, tissue- type-specific need enable serves distinguish them cells. population NKp46+NK1.1+ glands [33.Cortez tumor-associated [39.Dadi al.Cancer immunosurveillance innate-like 164: 365-377Abstract Salivary CD69 retention exhibit characteristic both ILCs: CD49b, expression, low IFN-γ production granule release, Scholar,40.Tessmer M.S. phenotypically functionally unique.PLoS Pathog. 7: e1001254Crossref One support TGF-β [35.Cortez Scholar,41.Gao al.Tumor immunoevasion effector 18: 1004-1015Crossref (182) methylcholanthrene (MCA)-induced fibrosarcoma model, promoted (CD49a−CD49b+) state (CD49a+CD49b+), finally noncytotoxic (CD49a+CD49b−) [41.Gao shown preventing melanoma MCA-tumor bearing TGF-β-driven putative mechanism tumors escape surveillance. Similarly, ablation (TGF-βR2, encoded Tgfbr2) Tgfbr2fl/fl × Ncr1cre led upregulation markers, WT findings seen gut. mediated obese model comparing lean [42.Cuff A.O. mediates nk less phenotype.Front. 10: 2180Crossref combination liver-specific phenotype. Thus, detailed analysis ILC1-specific would beneficial understand organs, reveal targets selective candidate therapeutics treat cell-mediated disease. controversial. existence prototypical CD127+ ieILC1 [43.Cooper M.A. biology killer-cell subsets.Trends 2001; 633-640Abstract (1846) described, CD49a+ (Table 1) [30.Fuchs Scholar,44.Cella al.Subsets ILC3−ILC1-like generate diversity tissues.Nat. 20: 980-991Crossref Scholar,45.Marquardt N. al.Identification intrahepatic 194: 2467-2471Crossref liver-unique displays cytotoxicity capacity [45.Marquardt counterpart Scholar,27.Gordon described tonsil gut, increased gut Crohn's disease CD127, cytotoxic, line this, SPADE-tree flow cytometry clustered separately [46.Sagebiel A.F. Eomes+ major infant intestine.Nat. 975Crossref (5) draining (LN), blood, marrow (BM), lung, recently confirmed high-dimensional healthy organ donors [47.Dogra P. determinants development, residence.Cell. 180: 749-763Abstract (10) Hence, (ieILC1) distributions, reflecting divergent microenvironment-dependent roles.Table 1Reported Human Markers Differential Expression Various TissuesaKey: + positive; negative; +/– heterogeneous; * [19]., bAbbreviations: (IL-7R-α); 1; ieILC1, ILC1; LN, node; n.d., determined..ILC1TissueT-betEomesCD56CD127CD49aCD103NKp44CD16CD69Liver
Language: Английский
Citations
144
The Journal of Experimental Medicine, Journal Year: 2021, Volume and Issue: 218(10)
Published: Aug. 25, 2021
Programs defining tissue-resident macrophage identity depend on local environmental cues. For alveolar macrophages (AMs), these signals are provided by immune and nonimmune cells include GM-CSF (CSF2). However, evidence to functionally link components of this intercellular cross talk remains scarce. We thus developed new transgenic mice profile pulmonary expression, which we detected in both cells, including group 2 innate lymphoid γδ T as well AT2s. AMs were unaffected constitutive deletion hematopoietic Csf2 basophil depletion. Instead, AT2 lineage-specific inducible revealed the nonredundant function AT2-derived instructing AM fate, establishing postnatal compartment, maintaining adult lungs. This AT2-AM relationship begins during embryogenesis, where nascent AT2s timely induce expression support proliferation differentiation fetal monocytes contemporaneously seeding tissue, persists into adulthood, when epithelial restricted
Language: Английский
Citations
113
Developmental Cell, Journal Year: 2021, Volume and Issue: 57(1), P. 112 - 145.e2
Published: Dec. 21, 2021
The human lung plays vital roles in respiration, host defense, and basic physiology. Recent technological advancements such as single-cell RNA sequencing genetic lineage tracing have revealed novel cell types enriched functional properties of existing lung. time has come to take a new census. Initiated by members the NHLBI-funded LungMAP Consortium aided experts biology community, we synthesized current data into comprehensive practical cellular census Identities normal are captured individual cards with delineation function, markers, developmental lineages, heterogeneity, regenerative potential, disease links, key experimental tools. This publication will serve starting point live, up-to-date guide for research at https://www.lungmap.net/cell-cards/. We hope that Lung CellCards promote community-wide effort establish, maintain, restore respiratory health.
Language: Английский
Citations
110
Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 22(11), P. 701 - 712
Published: March 30, 2022
Language: Английский
Citations
99
Science Immunology, Journal Year: 2022, Volume and Issue: 7(70)
Published: April 8, 2022
Innate lymphocytes are integral components of the cellular immune system that can coordinate host defense against a multitude challenges and trigger immunopathology when dysregulated. Natural killer (NK) cells innate lymphoid (ILCs) effectors postulated to functionally mirror conventional cytotoxic T helper cells, respectively. Here, we showed cytolytic molecule granzyme C was expressed in with phenotype type 1 ILCs (ILC1s) mouse liver salivary gland. Cell fate-mapping transfer studies revealed C-expressing could be derived from ILC progenitors did not interconvert NK ILC2s, or ILC3s. Granzyme defined maturation state ILC1s. These ILC1s required transcription factors T-bet and, lesser extent, Eomes support transforming growth factor-β (TGF-β) signaling for their maintenance In transgenic breast cancer model, depleting caused accelerated tumor growth. gained expression following interleukin-15 (IL-15) stimulation, which enabled perforin-mediated cytotoxicity. Constitutive activation STAT5, factor regulated by IL-15, triggered lethal perforin-dependent autoimmunity neonatal mice. Thus, marks effector ILC1s, broadening function beyond "helper-like" lymphocytes.
Language: Английский
Citations
75
Cell Reports, Journal Year: 2023, Volume and Issue: 42(2), P. 112073 - 112073
Published: Feb. 1, 2023
Type 2 T helper (Th2) cells and group innate lymphoid (ILC2s) provide protection against helminth infection are involved in allergic responses. However, their relative importance crosstalk during type immune responses still controversial. By generating utilizing mouse strains that deficient either ILC2s or Th2 cells, we report interleukin (IL)-33-mediated ILC2 activation promotes the cell response to papain; however, ovalbumin (OVA)/alum immunization is thymic stromal lymphopoietin (TSLP) dependent but independent of ILC2s. During infection, collaborate at different phases mainly through IL-4 production, induce expression IL-25, IL-33, TSLP, among which IL-25 IL-33 redundantly promote expansion. Thus, while differentiation can occur independently ILC2s, may responses, expand by inducing alarmins.
Language: Английский
Citations
44
Immunological Reviews, Journal Year: 2025, Volume and Issue: 330(1)
Published: Feb. 27, 2025
ABSTRACT Asthma is a common chronic inflammatory disease of the airways. A substantial number patients present with severe and therapy‐resistant asthma, for which underlying biological mechanisms remain poorly understood. In most asthma patients, airway inflammation characterized by activation type 2 immunity. CD4 + T helper (Th2) cells are canonical producers cytokines that fuel inflammation: interleukin (IL)‐4, IL‐5, IL‐9, IL‐13. However, more recent findings have shown other lymphocyte subsets, in particular group innate lymphoid (ILC2s) CD8 cytotoxic (Tc2) cells, can also produce large amounts cytokines. Importantly, inflammation, despite high sensitivity Th2 suppression corticosteroids—the mainstay drugs asthma. Emerging evidence indicates ILC2s Tc2 abundant adopt corticosteroid‐resistance states. Moreover, many do not overt implicating non‐type immunity as driver disease. this review, we will discuss pathophysiology focus on roles played ILC2s, lymphocytes, placing special emphasis forms.
Language: Английский
Citations
2
Immunity, Journal Year: 2020, Volume and Issue: 53(4), P. 775 - 792.e9
Published: Sept. 30, 2020
Language: Английский
Citations
121