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  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-5-30)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-5-30)
    Abstract: Group 2 innate lymphoid cells (ILC2s) were identified in 2010 as a novel lymphocyte subset lacking antigen receptors, such as T-cell or B-cell receptors. ILC2s induce local immune responses characterized by producing type 2 cytokines and play essential roles for maintaining tissue homeostasis. ILC2s are distributed across various organs, including the intestine where immune cells are continuously exposed to external antigens. Followed by luminal antigen stimulation, intestinal epithelial cells produce alarmins, such as IL-25, IL-33, and thymic stromal lymphopoietin, and activate ILC2s to expand and produce cytokines. In the context of parasite infection, the tuft cell lining in the epithelium has been revealed as a dominant source of intestinal IL-25 and possesses the capability to regulate ILC2 homeostasis. Neuronal systems also regulate ILC2s through neuropeptides and neurotransmitters, and interact with ILC2s bidirectionally, a process termed “neuro-immune crosstalk”. Activated ILC2s produce type 2 cytokines, which contribute to epithelial barrier function, clearance of luminal antigens and tissue repair, while ILC2s are also involved in chronic inflammation and tissue fibrosis. Recent studies have shed light on the contribution of ILC2s to inflammatory bowel diseases, mainly comprising ulcerative colitis and Crohn’s disease, as defined by chronic immune activation and inflammation. Modern single-cell analysis techniques provide a tissue-specific picture of ILC2s and their roles in regulating homeostasis in each organ. Particularly, single-cell analysis helps our understanding of the uniqueness and commonness of ILC2s across tissues and opens the novel research area of ILC2 heterogeneity. ILC2s are classified into different phenotypes depending on tissue and phase of inflammation, mainly inflammatory and natural ILC2 cells. ILC2s can also switch phenotype to ILC1- or ILC3-like subsets. Hence, recent studies have revealed the heterogeneity and plasticity of ILC2, which indicate dynamicity of inflammation and the immune system. In this review, we describe the regulatory mechanisms, function, and pathological roles of ILC2s in the intestine.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 2
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-10-4)
    Abstract: Group 2 innate lymphoid cells (ILC2s) serve as frontline defenses against parasites. However, excluding helminth infections, it is poorly understood how ILC2s function in intestinal inflammation, including inflammatory bowel disease.   Here, we analyzed the global gene expression of ILC2s in healthy and colitic conditions and revealed that type I interferon (T1IFN)-stimulated genes were up-regulated in ILC2s in dextran sodium sulfate (DSS)-induced colitis. The enhancement of T1IFN signaling in ILC2s in DSS-induced colitis was correlated with the downregulation of cytokine production by ILC2s, such as interleukin-5. Blocking T1IFN signaling during colitis resulted in exaggeration of colitis in both wild-type and Rag2 -deficient mice. The exacerbation of colitis induced by neutralization of T1IFN signaling was accompanied by reduction of amphiregulin (AREG) in ILC2s and was partially rescued by exogenous AREG treatment. Collectively, these findings show the potential roles of T1IFN in ILC2s that contribute to colitis manifestation.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 3
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-10-24)
    Abstract: Cytotoxic CD4 + T cells (CD4-CTLs) show the presence of cytolytic granules, which include the enzymes granzyme and perforin. The cells have a pathogenic and protective role in various diseases, including cancer, viral infection, and autoimmune disease. In mice, cytotoxic CD4 + T cells express CD8αα + and reside in the intestine (mouse CD4 + CTLs; mCD4-CTLs). The population of cytotoxic CD4 + T cells in the human intestine is currently unknown. Moreover, it is unclear how cytotoxic CD4 T cells change in patients with inflammatory bowel disease (IBD). Here, we aimed to identify cytotoxic CD4 + T cells in the human intestine and analyze the characteristics of the population in patients with IBD using single-cell RNA-seq (scRNA-seq). In CD4 + T cells, granzyme and perforin expression was high in humanMAIT (hMAIT) cells and hCD4 + CD8A + T cell cluster. Both CD4 and CD8A were expressed in hTreg, hMAIT, and hCD4 + CD8A + T cell clusters. Next we performed fast gene set enrichment analysis to identify cell populations that showed homology to mCD4CTLs. The analysis identified the hCD4 + CD8A + T cell cluster (hCTL-like population; hCD4-CTL) similar to mouse CTLs. The percentage of CD4 + CD8A + T cells among the total CD4 + T cells in the inflamed intestine of the patients with Crohn’s disease was significantly reduced compared with that in the noninflamed intestine of the patients. In summary, we identified cytotoxic CD4 + CD8 + T cells in the small intestine of humans. The integration of the mouse and human sc-RNA-seq data analysis highlight an approach to identify human cell populations related to mouse cell populations, which may help determine the functional properties of several human cell populations in mice.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2017
    In:  Frontiers in Immunology Vol. 8 ( 2017-11-13)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 8 ( 2017-11-13)
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2017
    detail.hit.zdb_id: 2606827-8
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