PLZF induces an intravascular surveillance program mediated by long-lived LFA-1–ICAM-1 interactions

Thomas, Seddon Y.; Scanlon, Seth Thomas; Griewank, Klaus G.; Constantinides, Michael G.; Savage, Adam K.; Barr, Kenneth; Meng, Fanyong; Luster, Andrew D.; Bendelac, Albert

doi:10.1084/jem.20102630

Cited by 164 publications

(201 citation statements)

References 52 publications

(76 reference statements)

Supporting

Mentioning

187

Contrasting

Unclassified

Order By: Relevance

“…8B). Furthermore, in line with previous results [21] the number of liver iNKT cells in B6 WT mice dropped up to three-fold after the combined application of anti-LFA-1 and anti-ICAM-1 antibodies. In slp-76 ace/ace mice, however, the respective reduction of iNKT cells was not higher than 2-fold (data not shown).…”

Section: Icam-1 Binds Preferably To Lfa-1 + Inkt Cellssupporting

confidence: 92%

“…Although individual iNKT cell subsets exhibit diverse functions, they still share molecules for tissue migration and adhesion [20,21,64]. Thus, the iNKT cell phenotype in slp-76 ace/ace mice might result from an altered trafficking and/or homing rather than a developmental selection and/or polarization process.…”

Section: Slp-76 Requires Adap For the Regulation Of Lfa-1-and Cd11b-mentioning

confidence: 99%

“…In contrast, there was an organ-specific reduction of LFA-1-expression on slp-76 ace/ace iNKT cells (Fig. 5A), particularly in the peripheral lymph nodes, but not in the liver, where LFA-1 had been implicated in the recruitment of iNKT cells [21,64]. Thus, additional molecules might be involved in the organ distribution of iNKT cells.…”

mentioning

confidence: 99%

“…The chemokine receptor CXCR6 and the integrin LFA-1, for example, promote the accumulation of iNKT cells in the livers and lungs [20,21]. While CXCR6 interacts with CXCL16, the heterodimeric integrins LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) interact with ICAM-1 [22][23][24].…”

mentioning

confidence: 99%

See 3 more Smart Citations

A mutation within the SH2 domain of slp‐76 regulates the tissue distribution and cytokine production of iNKT cells in mice

et al. 2016

View full text Add to dashboard Cite

TCR ligation is critical for the selection, activation, and integrin expression of T lymphocytes. Here, we explored the role of the TCR adaptor protein slp-76 on iNKT-cell biology. Compared to B6 controls, slp-76 ace/ace mice carrying a missense mutation (Thr428Ile) within the SH2-domain of slp-76 showed an increase in iNKT cells in the thymus and lymph nodes, but a decrease in iNKT cells in spleens and livers, along with reduced ADAP expression and cytokine response. A comparable reduction in iNKT cells was observed in the livers and spleens of ADAP-deficient mice. Like ADAP −/− iNKT cells, slp-76 ace/ace iNKT cells were characterized by enhanced CD11b expression, correlating with an impaired induction of the TCR immediate-early gene Nur77 and a decreased adhesion to ICAM-1. Furthermore, CD11b-intrinsic effects inhibited cytokine release, concanavalin A-mediated inflammation, and iNKT-cell accumulation in the liver. Unlike B6 and ADAP −/− mice, the expression of the transcription factors Id3 and PLZF was reduced, whereas NP-1-expression was enhanced in slp-76 ace/ace mice. Blockade of NP-1 decreased the recovery of iNKT cells from peripheral lymph nodes, identifying NP-1 as an iNKT-cell-specific adhesion factor. Thus, slp-76 contributes to the regulation of the tissue distribution, PLZF, and cytokine expression of iNKT cells via ADAP-dependent and -independent mechanisms.Keywords: ADAP r Cytokine r iNKT cell r Integrin r slp-76Additional supporting information may be found in the online version of this article at the publisher's web-site Eur. J. Immunol. 2016Immunol. . 46: 2121Immunol. -2136 Introduction iNKT cells express a panoply of NK-cell receptors [1] and a canonical TCR through which they recognize (glyco-)lipid antigens [2]. iNKT cells activate similar signaling cascades after TCR ligation like other T lymphocytes [3], but utilize unique transcription factors for their development such as the promyelocytic leukemia zinc finger (PLZF) [4][5][6]. According to two different developmental models PLZF characterizes distinct maturation stages and polarized subsets. The sequential lineage model suggests a gradual decrease of PLZFexpression following selection of iNKT cells which show a Th2-dominated cytokine profile during earlier and a Th1-dominated cytokine profile during later stages of intrathymic maturation [1,7]. The second model describes lineage diversification and simultaneous differentiation into Th1-, Th2-, or Th17-polarized subsets that are defined by the level of PLZF-expression [8]. Although many iNKT cells release both Th1 and Th2 cytokines on a single cell level [9], the production of IL-17 and IFN-γ is mutually exclusive within NK1.1 − cells [10][11][12]. Several transcription factors, such as Egr2, T-bet, ThPOK, Id2, Id3, and the Tec kinases Itk and Rlk have been implicated in the differentiation of iNKT cell subsets [6,8,[13][14][15][16][17] which home to distinct tissues. Specifically, liver and spleen constitute the main source for the Th1-polarized sublineage which is PLZF low . Th2-or ...

show abstract

Section: Icam-1 Binds Preferably To Lfa-1 + Inkt Cellssupporting

confidence: 92%

Section: Slp-76 Requires Adap For the Regulation Of Lfa-1-and Cd11b-mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

A mutation within the SH2 domain of slp‐76 regulates the tissue distribution and cytokine production of iNKT cells in mice

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Les cellules NK, présentes en grand nombre dans les organes non lymphoïdes comme le foie ou les poumons, retournent-elles périodiquement dans la circulation sanguine ou meurent-elles in situ et sont-elles remplacées par de nouvelles cellules immigrantes ? Un article récent a analysé l'échange de cellules NK entre souris congéniques parabiotiques (c'est-à-dire dont les circulations sanguines ont été fusionnées, mais en s'assurant que les cellules sanguines de chacun des partenaires pouvaient être distinguées) un mois après la parabiose [13]. Cette étude révèle que le principe de « vases communicants » s'applique aux populations NK du sang, de la rate et du poumon qui se répartissent équitablement (50/50) entre les deux partenaires.…”

Section: Recirculation Des Cellules Nkunclassified

Homéostasie des cellulesnatural killer

et al. 2012

View full text Add to dashboard Cite

CD1d ‐Restricted Natural Killer T Cells

Hill

Bezbradica

Kaer

et al. 2016

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Natural killer T (NKT) cells that express the semi‐invariant T‐cell receptor are innate‐like lymphocytes whose functions are controlled by self and foreign glycolipid ligands. Such ligands are presented by the antigen‐presenting, MHC class I‐like molecule CD1d, which belongs to a family of lipid antigen‐presenting molecules collectively called CD1. Activation of NKT cells in vivo results in rapid release of copious amounts of effector cytokines and chemokines with which they regulate innate and adaptive immune responses to pathogens, certain types of cancers and self‐antigens. The nature of CD1d‐restricted ligands, the manners in which they are recognised and the unique effector functions of NKT cells suggest an immunoregulatory role for this T‐cell subset. Their ability to respond fast and our ability to steer NKT cell cytokine responses to altered lipid ligands make them an important target for vaccine design and immunotherapies against autoimmune diseases. This article summarises our current understanding of CD1d‐restricted NKT cell biology and how these innate‐like lymphocytes control inflammation. Key Concepts CD1d molecules belong to a family of lipid antigen‐presenting molecules collectively called CD1. CD1d molecules resemble peptide antigen‐presenting MHC class I molecules. CD1d molecules restrict the specificity and functions of Natural killer T (NKT) cells. NKT cells recognise self‐ and nonself‐lipid ligands. Antigen recognition quickly activates NKT cells, which respond immediately by releasing proinflammatory and immunoregulatory cytokines and chemokines. Activated NKT cells communicate with cells of the innate and adaptive immune systems by cell–cell interactions and/or via soluble mediators. Such communications allow NKT cells to control immune responses to microbial pathogens and certain cancers. NKT‐cell activation has beneficial and, sometimes, adverse effects on certain autoimmune and metabolic disorders. NKT cells are targets for vaccine adjuvants and immunotherapies.

show abstract

PLZF induces an intravascular surveillance program mediated by long-lived LFA-1–ICAM-1 interactions

Abstract: PLZF-expressing NKT cells establish residence at intravascular locations, failing to enter the circulation because of constitutive interactions with LFA-1 and ICAM-1.

Cited by 164 publications

References 52 publications

A mutation within the SH2 domain of slp‐76 regulates the tissue distribution and cytokine production of iNKT cells in mice

A mutation within the SH2 domain of slp‐76 regulates the tissue distribution and cytokine production of iNKT cells in mice

Homéostasie des cellulesnatural killer

CD1d ‐Restricted Natural Killer T Cells

Contact Info

Product

Resources

About