Intra- and Intercompartmental Movement of γδ T Cells: Intestinal Intraepithelial and Peripheral γδ T Cells Represent Exclusive Nonoverlapping Populations with Distinct Migration Characteristics

Chennupati, Vijaykumar; Worbs, Tim; Liu, Xiaosun; Malinarich, Frano; Schmitz, Susanne; Haas, Julian; Malissen, Bernard; Förster, Reinhold; Prinz, Immo

doi:10.4049/jimmunol.1001652

Cited by 73 publications

(90 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some studies have shown that γδ IELs contribute to progression of immune-mediated colitis (5)(6)(7); other data suggest that γδ IELs contribute to mucosal homeostasis (8,9) by secreting keratinocyte growth factor (10,11) and antimicrobial peptides (12,13), suppressing CD4 + T-cell expansion through TGF-β and IL-10 production (8,9) and promoting barrier maintenance via poorly understood mechanisms (13)(14)(15). These observations and the small number of IELs relative to intestinal epithelial cells are difficult to reconcile with the widely held belief that γδ IELs have limited motility (1,16).…”

mentioning

confidence: 63%

“…Recent work demonstrated that γδ T-cell migration within axillary lymph nodes is rapid; however, the examination of intraepithelial γδ IEL migration could not be completely resolved from artifacts caused by residual peristaltic movement (16). In contrast, the approach used here stabilized an externalized loop of jejunum and allowed the villi to be imaged for up to 5 h with little extraneous movement.…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, IELs are generally perceived as being "sessile" (1) cells with "very limited basal motility" (16). Thus, it remains unclear how γδ T cells interact with the epithelium and mucosal microenvironment to impact intestinal biology.…”

Section: Discussionmentioning

confidence: 99%

“…Although trafficking of γδ T cells between extraintestinal sites and the intestinal intraepithelial compartment has been studied extensively (1,16,(31)(32)(33), intraepithelial migration has not been well characterized (16). Consequently, IELs are generally perceived as being "sessile" (1) cells with "very limited basal motility" (16).…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Dynamic migration of γδ intraepithelial lymphocytes requires occludin

Edelblum¹,

Shen²,

Weber³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

155

191

View full text Add to dashboard Cite

γδ intraepithelial lymphocytes (IELs) are located beneath or between adjacent intestinal epithelial cells and are thought to contribute to homeostasis and disease pathogenesis. Using in vivo microscopy to image jejunal mucosa of GFP γδ T-cell transgenic mice, we discovered that γδ IELs migrate actively within the intraepithelial compartment and into the lamina propria. As a result, each γδ IEL contacts multiple epithelial cells. Occludin is concentrated at sites of γδ IEL/epithelial interaction, where it forms a ring surrounding the γδ IEL. In vitro analyses showed that occludin is expressed by epithelial and γδ T cells and that occludin derived from both cell types contributes to these rings and to γδ IEL migration within epithelial monolayers. In vivo TNF administration, which results in epithelial occludin endocytosis, reduces γδ IEL migration. Further in vivo analyses demonstrated that occludin KO γδ T cells are defective in both initial accumulation and migration within the intraepithelial compartment. These data challenge the paradigm that γδ IELs are stationary in the intestinal epithelium and demonstrate that γδ IELs migrate dynamically to make extensive contacts with epithelial cells. The identification of occludin as an essential factor in γδ IEL migration provides insight into the molecular regulation of γδ IEL/epithelial interactions.intestine | tight junction T he intestine is one of the few peripheral tissues to contain a large population of intraepithelial lymphocytes (IELs), with one IEL for every 5-10 epithelial cells. Although the majority of these IELs express the γδ T cell receptor, and epidermal γδ IELs have been studied extensively (1-4), the functions of intestinal γδ IELs remain poorly understood. Some studies have shown that γδ IELs contribute to progression of immune-mediated colitis (5-7); other data suggest that γδ IELs contribute to mucosal homeostasis (8, 9) by secreting keratinocyte growth factor (10, 11) and antimicrobial peptides (12, 13), suppressing CD4 + T-cell expansion through TGF-β and IL-10 production (8, 9) and promoting barrier maintenance via poorly understood mechanisms (13-15). These observations and the small number of IELs relative to intestinal epithelial cells are difficult to reconcile with the widely held belief that γδ IELs have limited motility (1, 16).Further understanding of γδ IEL function will require definition of the molecular structures that regulate interactions between intestinal epithelial and γδ T cells. On the basis of the location of epithelial/γδ IEL contact sites along epithelial lateral membranes, it is likely that epithelial proteins targeted to these domains, including apical junction complex components, are involved in these interactions. Attractive candidates include E-cadherin, which can bind CD103 (α E β 7 integrin) expressed by IELs (17), as well as tight junction proteins. For example, γδ IELs express several epithelial tight junction proteins, including occludin and zonula occludens-1 (ZO-1) (18), that may bind directly or indirectly t...

show abstract

mentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Dynamic migration of γδ intraepithelial lymphocytes requires occludin

Edelblum¹,

Shen²,

Weber³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

155

191

View full text Add to dashboard Cite

show abstract

“…iIEL preparation iIELs were prepared as described previously (30), with minor modifications. In brief, the small intestine was harvested, flushed with cold HBSS supplemented with 5% FBS, and Peyer's patches were excised and opened longitudinally.…”

Section: Flow Cytometrymentioning

confidence: 99%

Notch Signaling Regulates the Homeostasis of Tissue-Restricted Innate-like T Cells

Chennupati

Koch

Coutaz

et al. 2016

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Although Notch signaling plays important roles in lineage commitment and differentiation of multiple cell types including conventional T cells, nothing is currently known concerning Notch function in innate-like T cells. We have found that the homeostasis of several well-characterized populations of innate-like T cells including invariant NKT cells (iNKT), CD8ααTCRαβ small intestinal intraepithelial lymphocytes, and innate memory phenotype CD8 T cells is controlled by Notch. Notch selectively regulates hepatic iNKT cell survival via tissue-restricted control of B cell lymphoma 2 and IL-7Rα expression. More generally, Notch regulation of innate-like T cell homeostasis involves both cell-intrinsic and -extrinsic mechanisms and relies upon context-dependent interactions with Notch ligand-expressing fibroblastic stromal cells. Collectively, using conditional ablation of Notch receptors on peripheral T cells or Notch ligands on putative fibroblastic stromal cells, we show that Notch signaling is indispensable for the homeostasis of three tissue-restricted populations of innate-like T cells: hepatic iNKT, CD8ααTCRαβ small intestinal intraepithelial lymphocytes, and innate memory phenotype CD8 T cells, thus supporting a generalized role for Notch in innate T cell homeostasis.

show abstract

Intravital Microscopy to Visualize Murine Small Intestinal Intraepithelial Lymphocyte Migration

Fischer

Edelblum

2022

Current Protocols

View full text Add to dashboard Cite

Intraepithelial lymphocytes (IELs) are critical sentinels involved in host defense and maintenance of the intestinal mucosal barrier. IELs expressing the γδ T‐cell receptor provide continuous surveillance of the villous epithelium by migrating along the basement membrane and into the lateral intercellular space between adjacent enterocytes. Intravital imaging has furthered our understanding of the molecular mechanisms by which IELs navigate the epithelial compartment and interact with neighboring enterocytes at steady state and in response to infectious or inflammatory stimuli. Further, evaluating IEL migratory behavior can provide additional insight into the nature and extent of cellular interactions within the intestinal mucosa. Three protocols describe methodology to visualize small intestinal IEL motility in real time using fluorescent reporter–transgenic mice and/or fluorophore‐conjugated primary antibodies and spinning‐disk confocal microscopy. Using Imaris image analysis software, a fourth protocol provides a framework to analyze IEL migration and quantify lymphocyte/epithelial interactions. Together, these protocols for intravital imaging and subsequent analyses provide the basis for elucidating the spatiotemporal dynamics of mucosal immune cells and interactions with neighboring enterocytes under physiological or pathophysiological conditions. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Mouse preparation and laparotomy Support Protocol: Antibody labeling of cell surface markers Basic Protocol 2: Image acquisition by spinning‐disk confocal microscopy Basic Protocol 3: 4D analysis of images

show abstract

Intra- and Intercompartmental Movement of γδ T Cells: Intestinal Intraepithelial and Peripheral γδ T Cells Represent Exclusive Nonoverlapping Populations with Distinct Migration Characteristics

Cited by 73 publications

References 61 publications

Dynamic migration of γδ intraepithelial lymphocytes requires occludin

Dynamic migration of γδ intraepithelial lymphocytes requires occludin

Notch Signaling Regulates the Homeostasis of Tissue-Restricted Innate-like T Cells

Intravital Microscopy to Visualize Murine Small Intestinal Intraepithelial Lymphocyte Migration

Contact Info

Product

Resources

About