Gammadelta T Cells in Crohn’s Disease: A New Player in the Disease Pathogenesis?

Catalán-Serra, Ignacio; Sandvik, Arne K.; Bruland, Torunn; Andreu‐Ballester, Juan Carlos

doi:10.1093/ecco-jcc/jjx039

Cited by 51 publications

(38 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Inflammatory Bowel Disease (IBD), psoriasis and asthma etc.) and neurodegeneration along with tissue homeostasis and repair [194][195][196][197][198][199]. γδT cells constitute minor (2%-10% of CD3 + T cells) but a very important component of the T-cell population in peripheral circulation in humans.…”

Section: Gamma Delta (γδ) T Cells In Inflammatory Diseases and Their mentioning

confidence: 99%

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Kumar

2018

International Immunopharmacology

501

346

View full text Add to dashboard Cite

The immune system is a very diverse system of the host that evolved during evolution to cope with various pathogens present in the vicinity of environmental surroundings inhabited by multicellular organisms ranging from achordates to chordates (including humans). For example, cells of immune system express various pattern recognition receptors (PRRs) that detect danger via recognizing specific pathogen-associated molecular patterns (PAMPs) and mount a specific immune response. Toll-like receptors (TLRs) are one of these PRRs expressed by various immune cells. However, they were first discovered in the Drosophila melanogaster (common fruit fly) as genes/proteins important in embryonic development and dorso-ventral body patterning/polarity. Till date, 13 different types of TLRs (TLR1-TLR13) have been discovered and described in mammals since the first discovery of TLR4 in humans in late 1997. This discovery of TLR4 in humans revolutionized the field of innate immunity and thus the immunology and host-pathogen interaction. Since then TLRs are found to be expressed on various immune cells and have been targeted for therapeutic drug development for various infectious and inflammatory diseases including cancer. Even, Single nucleotide polymorphisms (SNPs) among various TLR genes have been identified among the different human population and their association with susceptibility/resistance to certain infections and other inflammatory diseases. Thus, in the present review the current and future importance of TLRs in immunity, their pattern of expression among various immune cells along with TLR based therapeutic approach is reviewed.

show abstract

Section: Gamma Delta (γδ) T Cells In Inflammatory Diseases and Their mentioning

confidence: 99%

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Kumar

2018

International Immunopharmacology

501

346

View full text Add to dashboard Cite

show abstract

“…Investigations of γδ T cells within the intestinal mucosa of IBD patients have proven contradictory and inconclusive, with various studies showing increases, decreases, or no change in the number or proportion of γδ IELs present (reviewed by Catalan-Serra et al 2017[112]). It should also be noted that a number of these studies focused broadly on all γδ T cells in the mucosa rather than distinguishing between their precise location (i.e.…”

Section: Addressing the Differences Between Mice And Men: γδ Iels In Ibdmentioning

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

“…To achieve this, they are kept in an "activated, yet resting" state, ready for action, but tight control of this poised activation state is essential. 2 If this control is disrupted, T-IEL might potentially exacerbate the intestinal damage found in autoimmune and inflammatory bowel diseases (IBD) [21][22][23][24][25] such as Crohn's and coeliac disease. It is therefore of vital importance to understand which signals activate T-IEL cytotoxic responses, and which signals trigger their tissue reparative functions.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of activation of innate-like intraepithelial T lymphocytes

2020

View full text Add to dashboard Cite

Intraepithelial T lymphocytes (T-IEL) contain subsets of innate-like T cells that evoke innate and adaptive immune responses to provide rapid protection at epithelial barrier sites. In the intestine, T-IEL express variable T cell antigen receptors (TCR), with unknown antigen specificities. Intriguingly, they also express multiple inhibitory receptors, many of which are normally found on exhausted or antigen-experienced T cells. This pattern suggests that T-IEL are antigen-experienced, yet it is not clear where, and in what context, T-IEL encounter TCR ligands. We review recent evidence indicating TCR antigens for intestinal innate-like T-IEL are found on thymic or intestinal epithelium, driving agonist selection of T-IEL. We explore the contributions of the TCR and various costimulatory and co-inhibitory receptors in activating T-IEL effector functions. The balance between inhibitory and activating signals may be key to keeping these highly cytotoxic, rapidly activated cells in check, and key to harnessing their immune surveillance potential.

show abstract

Gammadelta T Cells in Crohn’s Disease: A New Player in the Disease Pathogenesis?

Cited by 51 publications

References 67 publications

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

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

Mechanisms of activation of innate-like intraepithelial T lymphocytes

Contact Info

Product

Resources

About