Transcription factor-driven regulation of ILC1 and ILC3

Schroeder, Jan-Hendrik; Howard, Jane K.; Lord, Graham M.

doi:10.1016/j.it.2022.04.009

Cited by 21 publications

(19 citation statements)

References 141 publications

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“…Some transcription factors, such as RORC, TBX21 and Notch (Figure 2G), are also essential for the differentiation of ILC subgroups. In the differentiation of human ILCs, some studies have found that the Notch→RORC→IL-23R pathway plays an important role, and these genes are expressed similarly in pig and human intestinal ILCs (Croft et al, 2022; Schroeder et al, 2022). At the same time, there is some specific expression of genes in porcine jejunum ILCs (Figure 5E).…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptional analysis of lamina propria lymphocytes in the jejunum reveals ILC-like cells in pigs

Wang

Cheng

Gao

et al. 2023

Preprint

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Pigs are the most suitable model to study various therapeutic strategies and drugs for human beings, while knowledge about tissue- and cell type-specific transcriptomes and heterogeneity is poorly available. Here, we focused on the intestinal immunity of pigs. Through single-cell sequencing (scRNA-seq) and flow cytometry analysis of the types of immune cells in the jejunum of pigs, we found that innate lymphoid cells (ILCs) existed in the lamina propria lymphocytes (LPLs) of the jejunum. Then, through flow sorting of Live/Dead (L/D)-Lineage(LIN)-CD45+ cells and scRNA-seq, we found that ILCs in the porcine jejunum were mainly ILC3s, with a small number of ILC1s, ILC2s and NK cells. Through a gene expression map, we found that ILCs coexpressed IL-7Rα, ID2 and other genes and differentially expressed RORC, GATA3 and other genes but did not express the CD3 gene. According to their gene expression profiles, ILC3s can be divided into four subgroups, and genes such as CXCL8, CXCL2, IL-22, IL-17 and NCR2 are differentially expressed. To further detect and identify ILC3s, we prepared RORC monoclonal antibodies and verified the classification of ILCs in the porcine jejunum subgroup and the expression of related hallmark genes at the protein level by flow cytometry. For systematically characterizing of ILCs in the porcin intestines, we combined our pigs ILCs dataset with publicly available humans and mice ILCs data and identified that the humans and pigs ILCs shared more common features than that of mice in gene signatures and cell states. Our results for the first time showed in detail the gene expression of porcine jejunal ILCs, the subtype classification of ILCs and the markers of various ILCs, which provides a basis for in-depth exploration of porcine intestinal mucosal immunity.

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Section: Discussionmentioning

confidence: 99%

Single-cell transcriptional analysis of lamina propria lymphocytes in the jejunum reveals ILC-like cells in pigs

Wang

Cheng

Gao

et al. 2023

Preprint

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“…Similarly, patients with Crohn’s disease have decreased levels of AhR, especially in the ileum, and have the tendency to convert ILC3 to type 1 innate lymphoid cells (ILC1) [ 143 , 144 ]. ILC1 elicits the production of IFNγ and TNFα, which are both known to induce apoptosis of epithelial cells in vitro, and most likely also in vivo, disrupting the intestinal barrier and increasing microbial-driven inflammation [ 145 ]. LC1 also induces TGFβ, which is associated with tumor formation and colorectal cancer (CRC) [ 145 ].…”

Section: Interkingdom Communicationmentioning

confidence: 99%

“…ILC1 elicits the production of IFNγ and TNFα, which are both known to induce apoptosis of epithelial cells in vitro, and most likely also in vivo, disrupting the intestinal barrier and increasing microbial-driven inflammation [ 145 ]. LC1 also induces TGFβ, which is associated with tumor formation and colorectal cancer (CRC) [ 145 ]. Further research is required to have a better understanding of the cross-talk between host AhR and bacterial QS molecules.…”

Section: Interkingdom Communicationmentioning

confidence: 99%

How does Quorum Sensing of Intestinal Bacteria Affect Our Health and Mental Status?

Dicks

2022

Microorganisms

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The human gut is host to almost 3000 microbial species, of which 90% are bacteria. Quorum sensing (QS) molecules generated by intestinal bacteria are important in establishing species- and strain-level structures within the gut microbiome but are also used to communicate with the host. Although we do not know which QS molecules have the most direct interaction with intestinal and sensory neurons, it is clear they affect our physiological and mental health. Signals produced by bacteria are diverse and include autoinducers (AIs), homoserine lactones (HSLs), quinolines, peptides, toxins and proteases. These signaling molecules activate specific receptors in the bacterial cell wall and trigger sensors in the cytoplasm that regulate gene expressions. A better understanding of the gene structures encoding the production of QS molecules is of importance when selecting strains with neurogenerative and other probiotic properties. Furthermore, QS molecules may be used as biomarkers in the diagnosis of inflammable bowel disease (IBD), irritable bowel syndrome (IBS) and colorectal cancer (CRC). In the future, it should be possible to use QS biomarkers to diagnose neurological and psychiatric diseases such as anxiety and depression, major depressive disorder (MDD), schizophrenia, bipolar disorder, autism and obsessive-compulsive disorder (OCD).

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“…However, the role for ILCs is far from being fully characterised, and much of the current knowledge has been gained from testing concepts that had previously been established for T and NK cell biology. As such, group 1, 2 and 3 ILC (ILC1, ILC2 and ILC3) express T-bet, GATA3 and RORγt, respectively, as characteristic transcription factors as well as cytokines associated with Th1, Th2 and Th17 cells (Bal et al ., 2020, Schroeder et al ., 2022). Due to the absence of TCR expression in ILC, these cells elicit immune functions in response to cytokines, chemokines and neurotransmitters, as has been well described for NK cells (Bal et al ., 2020, Klose et al ., 2020).…”

Section: Introductionmentioning

confidence: 99%

CD90 is not constitutively expressed in functional innate lymphoid cells

Schroeder

Zabinski

Neves

et al. 2021

Preprint

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Huge progress has been made in understanding the biology of innate lymphoid cells (ILC) by adopting several well-known concepts of T cell biology. As such flow cytometry gating strategies and markers, such as CD90, to identify ILC were discovered. Here we report that most non-NK intestinal ILC have a high expression of CD90 as expected, but surprisingly some have only a low or even no expression of this marker. CD90-negative CD127+ ILC were identified among all ILC subsets in the gut. CD90-negative cLP ILC2 were frequent at steady state. The frequency of CD90-negative CD127+ ILC was dependent on stimulatory cues in vitro and in vivo, and CD90-negative CD127+ ILC played a functional role as a source of IL-13, IFNγ and IL-17A at steady state and upon dextran sulphate sodium-elicited colitis. Hence, this study highlights for the first time that CD90 is not constitutively expressed by functional ILC in the gut.

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Transcription factor-driven regulation of ILC1 and ILC3

Cited by 21 publications

References 141 publications

Single-cell transcriptional analysis of lamina propria lymphocytes in the jejunum reveals ILC-like cells in pigs

Single-cell transcriptional analysis of lamina propria lymphocytes in the jejunum reveals ILC-like cells in pigs

How does Quorum Sensing of Intestinal Bacteria Affect Our Health and Mental Status?

CD90 is not constitutively expressed in functional innate lymphoid cells

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