Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ILC2s navigate tissue redistribution during infection using stage-specific S1P receptors [ATAC-seq]

ABSTRACT: Lymphocytes can circulate as well as take residence within tissues. The mechanisms by which circulating populations are recruited to infected tissue sites have been characterized, but the extent and molecular basis of tissue-resident cell recirculation is enigmatic. Here, we show that helminth infection- or IL-25-induced redistribution of intestinal tissue-localized group 2 innate lymphoid cells (ILC2s) requires access to the lymphatic vessel network even though secondary lymphoid structures, which are essential signal hubs for adaptive lymphocyte differentiation and dispatch, are dispensable for tissue ILC2 mobilization. IL-25 signals induce a dramatic change in epigenetic landscape of intestinal ILC2s, enabling the expression of sphingosine-1-phosphate (S1P) receptors. S1PR5 is critical for ILC2 exit from intestinal tissue to lymph, whereas S1PR1 plays a dominant role in ILC2 egress from mesenteric lymph nodes to blood circulation and then to lung, where redistributed ILC2s contribute to tissue repair. The requirement of two S1PRs is largely due to the dynamic expression of the tissue-retention marker CD69, which mediates S1PR1 internalization. This stage-specific requirement of different S1P receptors for ILC2 redistribution during infection illustrates that innate and adaptive lymphocytes share a circulatory network frame but employ specialized navigation cues for their distinct migratory requirements.

ORGANISM(S): Mus musculus

PROVIDER: GSE270373 | GEO | 2024/06/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

ILC2s navigate tissue redistribution during infection using stage-specific S1P receptors

Project description:Lymphocytes can circulate as well as take residence within tissues. The mechanisms by which circulating populations are recruited to infected tissue sites have been characterized, but the extent and molecular basis of tissue-resident cell recirculation is enigmatic. Here, we show that helminth infection- or IL-25-induced redistribution of intestinal tissue-localized group 2 innate lymphoid cells (ILC2s) requires access to the lymphatic vessel network even though secondary lymphoid structures, which are essential signal hubs for adaptive lymphocyte differentiation and dispatch, are dispensable for tissue ILC2 mobilization. IL-25 signals induce a dramatic change in epigenetic landscape of intestinal ILC2s, enabling the expression of sphingosine-1-phosphate (S1P) receptors. S1PR5 is critical for ILC2 exit from intestinal tissue to lymph, whereas S1PR1 plays a dominant role in ILC2 egress from mesenteric lymph nodes to blood circulation and then to lung, where redistributed ILC2s contribute to tissue repair. The requirement of two S1PRs is largely due to the dynamic expression of the tissue-retention marker CD69, which mediates S1PR1 internalization. This stage-specific requirement of different S1P receptors for ILC2 redistribution during infection illustrates that innate and adaptive lymphocytes share a circulatory network frame but employ specialized navigation cues for their distinct migratory requirements.

2024-06-05 | GSE268826 | GEO

Retinoic acid drives intestine-specific adaptation of effector ILC2s originating from distant sites [scRNA-Seq]

Project description:Adaptation of immune cells to tissue-specific microenvironments is a crucial process in homeostasis and inflammation. Here, we show that murine effector type 2 innate lymphoid cells (ILC2s) from various organs are equally effective in repopulating ILC2 niches in other anatomical locations where they adapt tissue-specific phenotypes of target organs. Single-cell transcriptomics of ILC2 populations revealed upregulation of retinoic acid (RA) signaling in ILC2s during adaptation to the small intestinal microenvironment, and RA signaling mediated reprogramming of kidney effector ILC2s towards the small intestinal phenotype in vitro and in vivo. Inhibition of intestinal ILC2 adaptation by blocking RA signaling impaired worm expulsion during Strongyloides ratti infection, indicating functional importance of ILC2 tissue imprinting. In conclusion, this study highlights that effector ILC2s retain the ability to adapt to changing tissue-specific microenvironments, enabling them to exert tissue-specific functions, such as promoting control of intestinal helminth infections.

2023-09-15 | GSE242569 | GEO

Retinoic acid drives intestine-specific adaptation of effector ILC2s originating from distant sites [bulk RNA-Seq]

2023-09-15 | GSE242562 | GEO

Epigenome analysis reveals novel aspects of ILC2 activation and supports a pathogenic role in asthma

Project description:Recent studies have shown that group 2 innate lymphoid cells (ILC2s) can drive eosinophilic airway inflammation in mouse models of asthma. Moreover, elevated ILC2 counts and/or activity have been reported in asthmatics, together suggesting that ILC2s play an important role in asthma pathophysiology. However, many aspects of ILC2 biology are not fully understood, including the mechanisms underlying ILC2 activation, the tissue-specific functions of ILC2s during inflammation (e.g. lung versus draining lymph node) and what drives ILC2 plasticity. Importantly, it is unknown whether human (epi)genetic variation associated with asthma susceptibility and persistence can be coupled to ILC2s. We address these questions in our manuscript by studying the epigenome of murine ILC2s obtained from Gata3-reporter mice with eosinophilic airway inflammation as well as human ILC2s obtained from peripheral blood and activated in vitro.

2018-03-14 | GSE98843 | GEO

Sphingosine 1-phosphate maintains naïve T cell by regulating apoptotic signaling

Project description:Effective immunity requires a large, diverse naïve T cell repertoire circulating among lymphoid organs in search of antigen. Sphingosine 1-phosphate (S1P) and its receptor S1PR1 contribute by both directing T cell migration and supporting T cell survival. Here, we address how S1P enables T cell survival, and the implications for patients treated with S1PR1 antagonists. Contrary to expectations, we found that S1PR1 limits apoptosis by maintaining the appropriate balance of BCL2 family members via restraint of JNK activity. Interestingly, the same residues of S1PR1 that enable receptor internalization are required to prevent JNK overactivation and limit apoptosis. Findings in mice were recapitulated in ulcerative colitis patients treated with the drug ozanimod, and the loss of naïve T cells limited B cell responses. Our findings highlight an unexpected effect of S1PR1 antagonists on the ability to mount immune responses within lymph nodes, beyond their effect on lymph node egress.

2024-02-21 | GSE221482 | GEO

Transcription factor Bcl11b controls identity and function of mature innate lymphoid cells type II

Project description:Type-2 innate lymphoid cells (ILC2s) promote anti-helminth responses and contribute to allergies. Though Bcl11b has been previously considered a T-lineage identity transcription factor (TF) that restrains the innate-cell genetic programs, we report here that Bcl11b is highly expressed in mature ILC2s and acts upstream of the key ILC2 TFs Gfi1, Gata-3, and of IL-33 receptor IL1rl1 (T1ST2). Additionally, Bcl11b-/- ILC2s de-repressed Rorγt, Ahr and IL-23 receptor, normally expressed in type-3 ILCs (ILC3s). Consequently, Bcl11b-/- ILC2s lost ILC2 functions and gained ILC3 functions, expanding in response to the protease allergen papain, however producing IL-17 and IL-22, and not IL-5 and IL-13, causing lung neutrophilia rather than eosinophilia, and diminished mucus production. Our results broaden Bcl11b's role from a T-cell only TF, and establishes that Bcl11b sustains mature ILC2 genetic and functional programs and lineage fidelity through positive regulation of essential ILC2 TFs and negative regulation of pivotal ILC3 TFs. RNA-seq analysis on sorted ILC2s from the mLNs of Bcl11bF/F Cre-ERT2 and wildtype mice at steady state following tamoxifen mediated deletion of Bcl11b

2015-07-28 | E-GEOD-67437 | biostudies-arrayexpress

Expression data from naive, effector and memory-like ILC2s isolated from mouse lungs and those from effector and memory-like ILC2s isolated from mediastinal lymph node

Project description:Group 2 innate lymphoid cells (ILC2s) in the lung are stimulated by inhaled allergens. ILC2s do not directly recognize allergens but they are stimulated by cytokines including interleukin (IL)-33 released by damaged epithelium.Lung ILC2s, upon stimulation, produce T helper 2 cell-type cytokines inducing T cell independent allergic lung inflammation. We now report that lung ILC2s, upon activation by an allergen or IL-33, acquire the properties of memory cells. The activated ILC2s initially proliferate and secrete cytokines, followed by a contraction phase as they stop producing cytokines. Nevertheless, some persist long after the resolution of the inflammation and acquire intrinsic capacities to react to unrelated allergens more vigorously than naÃ¯ve ILC2s, thus mediating a severe allergic lung inflammation. Gene expression profiles of the previously activated ILC2s show a gene signature of memory T cells. These antigen non-specific memory ILC2s may explain why asthma patients are often sensitized to multiple allergens. ILC2s were isolated from mouse lungs from naive and IL-33 injected mice 4 days, 14 days and 4 months after the initial treatment. RNA was extracted from those ILC2 populations and analyzed for gene expression profiles. RNA was also extracted from ILC2s isolated from lung draining mediastinal lymph node (mLN) 4 days and 14 days after IL-33 treatment.

2016-06-30 | E-GEOD-81700 | biostudies-arrayexpress

S1P-dependent inter-organ trafficking of group 2 innate lymphoid cells supports host defense

Project description:Innate lymphoid cells (ILCs) are considered to be the innate counterparts of adaptive T lymphocytes and play important roles in host defense, tissue repair, metabolic homeostasis, and inflammatory diseases. ILCs are generally thought of as tissue-resident cells, but whether ILCs strictly behave in a tissue-resident manner or can move between sites during infection is unclear. We show here that IL-25- or helminthic infection-induced inflammatory ILC2s are not tissue-resident but circulating cells, which arise from resting ILC2s residing in intestinal lamina propria and then migrate to mesenteric lymph nodes, spleen, lung, and liver. IL-25 induces rapid proliferation of the intestinal ILC2s and a change in their sensitivity to S1P-mediated chemotaxis, leading to lymphatic entry, blood circulation, and accumulation in periphery sites, including the lung where they contribute to anti-helminth defense and tissue repair. Our finding of cytokine-driven expansion and migration of innate lymphocytes, a behavioral parallel to the antigen-driven priming, expansion, and migration of adaptive lymphocytes to effector sites in distant tissues, provides a significant advance in our overall understanding of ILCs and indicates that ILCs complement adaptive immunity by providing both local and distant site effector protection during infection.

2018-01-08 | GSE104708 | GEO

Homeostatic leukotrienes, IL-25, and IL-33 signals on intestinal ILC2 status

Project description:We report the high-throughput profiling of murine intestinal type 2 innate lymphoid cells (ILC2) transcriptome. By obtaining over 8.7 million bases of sequence, we generated genome-wide expression maps of mouse ILC2 without the presense of known activation signals(IL-25, IL-33 receptor) and new non-redundant signal (leukotriene). We find that homeostatic signaling minimally contributes to intestinal ILC2 activation statu. 500 ILC2s were sorted as CD45+Lineage-IL-17RB+

2020-02-16 | GSE144956 | GEO

Project description:ILC2s navigate tissue redistribution during infection using stage-specific S1P receptors

| PRJNA1112564 | ENA