Detection of Rare Antigen-Presenting Cells through T Cell-Intrinsic Meandering Motility, Mediated by Myo1g

Gérard, Audrey; Patiño-López, Genaro; Beemiller, Peter; Nambiar, Rajalakshmi; Ben-Aissa, Khadija; Yin, Liu; Totah, Fadi J.; Tyska, Matthew J.; Shaw, Stephen; Krummel, Matthew F.

doi:10.1016/j.cell.2014.05.044

Cited by 113 publications

(126 citation statements)

References 66 publications

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“…It remains possible that TCR signaling additionally interferes with molecular motors that are known to profoundly impact T-cell motility. During steady-state migration, decreased myosin-IIA activity has been reported to promote an adhesive mode of crawling (16), whereas increased myosin-IG activity has been shown to favor direction changes (24).…”

Section: Discussionmentioning

confidence: 99%

Signal strength regulates antigen-mediated T-cell deceleration by distinct mechanisms to promote local exploration or arrest

Moreau

Lemaı̂tre

Garrod

et al. 2015

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

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International audienceT lymphocytes are highly motile cells that decelerate upon antigen recognition. These cells can either completely stop or maintain a low level of motility, forming contacts referred to as synapses or kinapses, respectively. Whether similar or distinct molecular mechanisms regulate T-cell deceleration during synapses or kinapses is unclear. Here, we used microfabricated channels and intravital imaging to observe and manipulate T-cell kinapses and synapses. We report that high-affinity antigen induced a pronounced deceleration selectively dependent on Ca 2+ signals and actin-related protein 2/3 complex (Arp2/3) activity. In contrast, low-affinity antigens induced a switch of migration mode that promotes T-cell exploratory behavior, characterized by partial deceleration and frequent direction changes. This switch depended on T-cell receptor binding but was largely independent of downstream signaling. We propose that distinct mechanisms of T-cell deceleration can be triggered during antigenic recognition to favor local exploration and signal integration upon suboptimal stimulus and complete arrest on the best antigen-presenting cells

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Section: Discussionmentioning

confidence: 99%

Signal strength regulates antigen-mediated T-cell deceleration by distinct mechanisms to promote local exploration or arrest

Moreau

Lemaı̂tre

Garrod

et al. 2015

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

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“…During the negative selection processes, SP cells exhibit confined migration paths (11) that support efficient Ag scanning (50,51), However regulation of the confined migration is still unknown. In this study, sema3e hi cells were scattered throughout the medulla and directional migration was increased in plexin D1 2/2 SP cells.…”

Section: Discussionmentioning

confidence: 99%

Sema3e/Plexin D1 Modulates Immunological Synapse and Migration of Thymocytes by Rap1 Inhibition

Ueda

Kondo

Ozawa

et al. 2016

The Journal of Immunology

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Regulation of thymocyte trafficking plays an important role during thymic selection, but our understanding of the molecular mechanisms underlying these processes is limited. In this study, we demonstrated that class III semaphorin E (sema3e), a guidance molecule during neural and vascular development, directly inhibited Rap1 activation and LFA-1–dependent adhesion through the GTPase-activating protein activity of plexin D1. Sema3e inhibited Rap1 activation of thymocytes in response to chemokines and TCR stimulation, LFA-mediated adhesion, and T cell–APC interactions. Immunological synapse (IS) formation in mature thymocytes on supported lipid bilayers was also attenuated by sema3e. Impaired IS formation was associated with reduced Rap1 activation on the contact surface and cell periphery. Moreover, a significant increase of CD4+ thymocytes was detected in the medulla of mice with T cell lineage–specific deletion of plexin D1. Two-photon live imaging of thymic explants and slices revealed enhanced Rap1 activation and migration of CD69+ double-positive and single-positive cells with plexin D1 deficiency. Our results demonstrate that sema3e/plexin D1 modulates IS formation and Ag-scanning activities of thymocytes within thymic tissues.

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“…In particular, loci cg07826859 (MYO1G) and cg19859270 (GPR15) have been reported to play a role in the formation of chronic inflammation via regulating the activity of T cells. 32,33 Locus cg25189904 is located on the south shore of a CpG island spanning the promoter of GNG12 that has been suggested to be an important factor in the overall inflammatory signaling cascade. 34 Moreover, another 3 loci are mapped to genes linked to the risks of various age-related cancers.…”

Section: Discussionmentioning

confidence: 99%

Tobacco smoking and smoking-related DNA methylation are associated with the development of frailty among older adults

et al. 2017

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Tobacco smoking is a preventable environmental factor that contributes to a wide spectrum of age-related health outcomes; however, its association with the development of frailty is not yet well established. We examined the associations of self-reported smoking indicators, serum cotinine levels and smoking-related DNA methylation biomarkers with a quantitative frailty index (FI) in 2 independent subsets of older adults (age 50-75) recruited in Saarland, Germany in 2000 -2002 (discovery set: n D 978, validation set: n D 531). We obtained DNA methylation profiles in whole blood samples by Illumina HumanMethylation450 BeadChip and calculated the FI according to the method of Mitnitski and Rockwood. Mixed linear regression models were implemented to assess the associations between smoking indicators and the FI. After controlling for potential covariates, current smoking, cumulative smoking exposure (pack-years), and time after smoking cessation (years) were significantly associated with the FI (P-value < 0.05). In the discovery panel, 17 out of 151 previously identified smoking-related CpG sites were associated with the FI after correction for multiple testing (FDR < 0.05). Nine of them survived in the validation phase and were designated as frailty-associated loci. A smoking index (SI) based on the 9 loci manifested a monotonic association with the FI. In conclusion, this study suggested that epigenetic alterations could play a role in smoking-associated development of frailty. The identified CpG sites have the potential to be prognostic biomarkers of frailty and frailty-related health outcomes. Our findings and the underlying mechanisms should be followed up in further, preferably longitudinal studies.

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Detection of Rare Antigen-Presenting Cells through T Cell-Intrinsic Meandering Motility, Mediated by Myo1g

Cited by 113 publications

References 66 publications

Signal strength regulates antigen-mediated T-cell deceleration by distinct mechanisms to promote local exploration or arrest

Signal strength regulates antigen-mediated T-cell deceleration by distinct mechanisms to promote local exploration or arrest

Sema3e/Plexin D1 Modulates Immunological Synapse and Migration of Thymocytes by Rap1 Inhibition

Tobacco smoking and smoking-related DNA methylation are associated with the development of frailty among older adults

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