Development of TCR.ALPHA..BETA. CD8.ALPHA..ALPHA. Intestinal Intraepithelial Lymphocytes Is Promoted by Interleukin-15-Producing Epithelial Cells Constitutively Stimulated by Gram-Negative Bacteria via TLR4

Kaneko, Masahiro; Mizunuma, Tsunehide; Takimoto, Hiroaki; Kumazawa, Yoshio

doi:10.1248/bpb.27.883

Cited by 18 publications

(10 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Discussionmentioning

confidence: 99%

“…In mucosal immunity, these two ILs are thought to be the regulatory factor to IEL differentiation by IEC [3][4][5]. Kaneko et al [4] reported that IEC-derived IL-15 could promote the development of TCRαβ+CD8α+CD8β− IEL. Yu et al [44] demonstrated that the introduction of IL-15 transgene into MyD88(−/−) mice partly restored the numbers of TCRαβ+ CD8α+CD8β− and TCRγδ+ IELs, which were reduced because of the lack of MyD88 and IEC-derived IL-15.…”

Section: Discussionmentioning

confidence: 99%

“…It stimulates differentiation of CD8 T cells and NK cells and, thus, has a role in lymphoid development and hemostasis [2]. It also regulates the development of intestinal intraepithelial lymphocytes (IELs) and is an immunoregulator in gut immune barrier function [3][4][5]. IELs are the innermost layer of gut-associated lymphoid tissue (GALT).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inhibitory effect of dietary n-3 polyunsaturated fatty acids to intestinal IL-15 expression is associated with reduction of TCRαβ+CD8α+CD8β− intestinal intraepithelial lymphocytes

Jian

Zhang

et al. 2008

The Journal of Nutritional Biochemistry

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibitory effect of dietary n-3 polyunsaturated fatty acids to intestinal IL-15 expression is associated with reduction of TCRαβ+CD8α+CD8β− intestinal intraepithelial lymphocytes

Jian

Zhang

et al. 2008

The Journal of Nutritional Biochemistry

View full text Add to dashboard Cite

“…Contrary to TLR induction of epithelial IL-15,[68, 67] reduced IEL number in Nod2 knockout mice was attributed to defective IL-15 production by myeloid cells. [66] Since IELs are in close proximity to both luminal sampling antigen-presenting cells and enterocytes, it stands to reason that multiple levels of regulation and crosstalk may inform IEL function and vice versa.…”

Section: Commensal Bacteria Influence Iel Development and Functionmentioning

confidence: 99%

Sentinels at the Frontline: the Role of Intraepithelial Lymphocytes in Inflammatory Bowel Disease

Edelblum

2017

Curr Pharmacol Rep

View full text Add to dashboard Cite

Purpose of review Intestinal mucosal immunity is tightly regulated to ensure effective host defense against invasive microorganisms while limiting the potential for aberrant damage. In inflammatory bowel disease (IBD), an imbalance between effector and regulatory T cell populations results in an uncontrolled inflammatory response to commensal bacteria. Intraepithelial lymphocytes (IEL) are perfectly positioned within the intestinal epithelium to provide the first line of mucosal defense against luminal microbes or rapidly respond to epithelial injury. This review will highlight how IELs promote protective intestinal immunity and discuss the evidence indicating that altered IEL responses contribute to the pathogenesis of IBD. Recent findings Although the role of IELs in mucosal homeostasis has been largely underappreciated, many of the same factors that contribute to the dysregulation of host defense in IBD also adversely affect IELs. For example, IL-23 and the endoplasmic reticulum stress response can enhance IEL lytic activity toward enterocytes. Microbial dysbiosis or defective microbial recognition results in the loss of regulatory IELs, further amplifying these pro-inflammatory effects. Migration of T cells into or within the intraepithelial compartment has a profound effect on their differentiation or effector function demonstrating that IELs are exquisitely sensitive to changes in the local intestinal microenvironment. Summary Enhanced mechanistic insight into the regulation of IEL survival, differentiation and effector function may provide useful tools to modulate IEL surveillance or enhance IEL regulatory function. Elucidation of these processes may result in the development of novel therapeutics to reduce intestinal inflammation and reinforce the mucosal barrier in IBD.

show abstract

“…Similarly, transgene epithelial Il‐7 expression restores extrathymic development of TCRγδ + IELs in the intestine of Il‐7‐deficient mice [77,79]. Both Il‐7 and Il‐15 expression have previously been associated with microbial exposure [80,81]. Also, IEC‐derived Il‐5 or eotaxin enhance eosinophils resident in the gut, as shown in transgene animals [82], but the endogenous regulation of intestinal epithelial Il‐5 and eotaxin expression under homeostatic conditions is ill‐defined.…”

Section: Maintenance Of Homeostasis and Barrier Integritymentioning

confidence: 99%

Innate immune signalling at the intestinal epithelium in homeostasis and disease

2012

View full text Add to dashboard Cite

The intestinal epithelium-which constitutes the interface between the enteric microbiota and host tissues-actively contributes to the maintenance of mucosal homeostasis and defends against pathogenic microbes. The recognition of conserved microbial products by cytosolic or transmembrane pattern recognition receptors in epithelial cells initiates signal transduction and influences effector cell function. However, the signalling pathways, effector molecules and regulatory mechanisms involved are not yet fully understood, and the functional outcome is poorly defined. This review analyses the complex and dynamic role of intestinal epithelial innate immune recognition and signalling, on the basis of results in intestinal epithelial cell-specific transgene or gene-deficient animals. This approach identifies specific epithelial cell functions within the diverse cellular composition of the mucosal tissue, in the presence of the complex and dynamic gut microbiota. These insights have thus provided a more comprehensive understanding of the role of the intestinal epithelium in innate immunity during homeostasis and disease.

show abstract

Development of TCR.ALPHA..BETA. CD8.ALPHA..ALPHA. Intestinal Intraepithelial Lymphocytes Is Promoted by Interleukin-15-Producing Epithelial Cells Constitutively Stimulated by Gram-Negative Bacteria via TLR4

Cited by 18 publications

References 40 publications

Inhibitory effect of dietary n-3 polyunsaturated fatty acids to intestinal IL-15 expression is associated with reduction of TCRαβ+CD8α+CD8β− intestinal intraepithelial lymphocytes

Inhibitory effect of dietary n-3 polyunsaturated fatty acids to intestinal IL-15 expression is associated with reduction of TCRαβ+CD8α+CD8β− intestinal intraepithelial lymphocytes

Sentinels at the Frontline: the Role of Intraepithelial Lymphocytes in Inflammatory Bowel Disease

Innate immune signalling at the intestinal epithelium in homeostasis and disease

Contact Info

Product

Resources

About