Heterogeneity of Endothelial Cells from Different Organ Sites in T-Cell Subset Recruitment

Lim, Yaw-Chyn; García‐Cardeña, Guillermo; Allport, Jennifer R.; Zervoglos, Mandy; Connolly, Andrew J.; Gimbrone, Michael A.; Luscinskas, Francis W.

doi:10.1016/s0002-9440(10)64293-9

Cited by 140 publications

(139 citation statements)

References 47 publications

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“…To assess whether the differential expression of VCAM was also present in Aire -/-endothelial cells, we purified mouse lung endothelial cells (MLEC) from Aire -/-and Aire +/+ mice and stimulated them for 16 h with increasing concentrations of IL-4. It has previously been described that the percentage of constitutively VCAM-expressing MLEC is low [47]. When investigating MLEC from Aire-sufficient mice, a low number of VCAM-1-expressing cells were found (14.4%), but the number of VCAM-1-expressing cells from Aire-deficient mice was significantly higher (17.3%) (Fig.…”

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confidence: 71%

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Increased antigen presenting cell‐mediated T cell activation in mice and patients without the autoimmune regulator

et al. 2006

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Patients with autoimmune polyendocrine syndrome type I (APS I)suffer from endocrine and non-endocrine disorders due to mutations in the autoimmune regulator gene (AIRE). Mouse Aire is expressed both in thymic medullary epithelial cells and in peripheral antigen-presenting cells, suggesting a role in both central and peripheral tolerance. We here report that Aire -/-dendritic cells (DC) activate naive T cells more efficiently than do Aire +/+ DC. Expression array analyses of Aire -/-DC revealed differential regulation of 68 transcripts, among which, the vascular cell adhesion molecule-1 (VCAM-1) transcript was up-regulated in Aire -/-DC. Concurrently, the expression of the VCAM-1 protein was up-regulated on both Aire -/-DC and monocytes from APS I patients. Blocking the interaction of VCAM-1 prevented enhanced Aire -/-DC stimulation of T cell hybridomas. We determined an increased number of DC in spleen and lymph nodes and of monocytes in the blood from Aire -/-mice, and an increased number of blood monocytes in APS I patients. Our findings imply a role for Aire in peripheral DC regulation of T cell activation, and suggest that Aire participates in peripheral tolerance.Supporting information for this article is available at http://www.wiley-vch.de/contents/jc_2040/2006/35240_s.pdf IntroductionInactivation of the autoimmune regulator gene (AIRE) [1][2][3] causes autoimmunity in patients with autoimmune polyendocrine syndrome type I (APS I, APECED, OMIM 240300) and in a gene targeted mouse model [4,5]. APS I is a rare monogenic autosomal recessive disease without HLA association [6,7], which is prevalent in isolated populations [8][9][10]. APS I patients develop a progressive loss of tolerance against self antigens and suffer from multiorgan failures due to the immunological destruction of adrenals, parathyroid glands and b cells of the islets of Langerhans [11]. Many of the APS I organ-specific autoantigens have been identified and characterized [12,13]. In addition, as a sign of immune dysfunction, these patients have difficulties clearing Candida albicans infections in mucosal membranes [14]. Functional studies of AIRE suggest a role as a transcription factor and in vitro transactivating studies support this notion [15][16][17][18]. Moreover, the PHD1 domain of AIRE has been suggested to have an E3 ubiquitin ligase activity in cell-free assays [19], findings in variance with a recent report [20]. Aire is highly expressed in a subset of the medullary thymic epithelial cells (mTEC) as well as in DC in the spleen and lymph nodes [21][22][23][24], indicating a potential role in immunological tolerance.To characterize the function of Aire, we previously engineered an Aire-deficient mouse targeting the most common APS I mutation [4]. Aire-deficient mice develop multiple organ-specific autoantibodies and lymphocytic infiltrates, thus mimicking some of the features of human APS I [4]. Subsequently, the role of Aire in negative selection was demonstrated [5]. These findings were further supported using TCR transgenic mic...

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confidence: 71%

“…To isolate murine lung endothelial cells, we modified a published protocol [47]. Briefly, lungs from Aire-deficient and Aire-sufficient mice were rinsed in DMEM containing 20% FCS, moved to a small petri dish and perfused with 2 mL collagenase (1 mg/mL) in serum-free DMEM.…”

Section: Isolation and In Vitro Culture Of Murine Lung Endothelial Cellsmentioning

confidence: 99%

Increased antigen presenting cell‐mediated T cell activation in mice and patients without the autoimmune regulator

et al. 2006

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“…ECs were isolated from hearts and lungs of C57BL/6 8-week-old, male mice (Charles River Laboratories, Wilmington, Mass) as previously described by Lim et al 26 In all experiments, cells from both hearts and lungs were mixed and used simultaneously. Mouse CMs were isolated by modifying the protocol for rat neonatal CMs as previously described by Wang et al 27 In brief, primary cultures were obtained from 1-to 2-day-old C57BL/6 mice by incubating mouse hearts in 0.1% trypsin in Hanks' buffered saline solution (both from Gibco BRL) for 7 hours, followed by digestion in 0.08% collagenase type II (Worthington) in Hanks' buffered saline solution.…”

Section: Cell Isolationmentioning

confidence: 99%

Endothelial Cells Promote Cardiac Myocyte Survival and Spatial Reorganization

et al. 2004

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“…Mouse EC isolation from muscle and lung tissues was performed as we described, 25 followed by immunoselection and immortalization modified from the protocol described by Lim and colleagues. 29 For immunoselection, 10-l beads (per T-75 of mouse lung cells) were washed with 1 ml of buffer A (PBS ϩ 2% fetal bovine serum) for three times and resuspended in 100 l of buffer A. Ten l (10 g) of anti-mouse ICAM-2 or 10 l (10 g) of PE-CAM-1 were added and rocked at 4°C for 2 hours.…”

Section: Cell Culture and Cytokinesmentioning

confidence: 99%

Differential Functions of Tumor Necrosis Factor Receptor 1 and 2 Signaling in Ischemia-Mediated Arteriogenesis and Angiogenesis

Luo

et al. 2006

The American Journal of Pathology

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We have previously shown that tumor necrosis factor (TNF) acts via its two receptors TNFR1 and TNFR2 to elicit distinct signaling pathways in vascular endothelial cells (ECs). Here we used a femoral artery ligation model to demonstrate that TNFR1-knockout (KO) mice had enhanced, whereas TNFR2-KO had reduced, capacity in clinical recovery, limb perfusion, and ischemic reserve capacity compared with the wildtype mice. Consistently, ischemia-initiated collateral growth (arteriogenesis) in the upper limb and capillary formation and vessel maturation (angiogenesis) in the lower limb were enhanced in TNFR1-KO but were reduced in TNFR2-KO mice. Furthermore, our results suggest that vascular proliferation, but not infiltration of macrophages and lymphocytes, accounted for the phenotypic differences between the TNFR1-KO and TNFR2-KO mice. In wild-type animals TNFR2 protein in vascular endothelium was highly up-regulated in response to ischemia, leading to increased TNFR2-specific signaling as determined by the formation TNFR2-TRAF2 complex and activation of TNFR2-specific kinase Bmx/Etk. In isolated murine ECs, activation of TNFR2 induced nuclear factor-Bdependent reporter gene expression, EC survival, and migration. In contrast, activation of TNFR1 caused inhibition of EC migration and EC apoptosis. These data demonstrate that TNFR1 and TNFR2 play differential roles in ischemia-mediated arteriogenesis and angiogenesis, partly because of their opposite effects on EC survival and migration.

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Heterogeneity of Endothelial Cells from Different Organ Sites in T-Cell Subset Recruitment

Cited by 140 publications

References 47 publications

Increased antigen presenting cell‐mediated T cell activation in mice and patients without the autoimmune regulator

Increased antigen presenting cell‐mediated T cell activation in mice and patients without the autoimmune regulator

Endothelial Cells Promote Cardiac Myocyte Survival and Spatial Reorganization

Differential Functions of Tumor Necrosis Factor Receptor 1 and 2 Signaling in Ischemia-Mediated Arteriogenesis and Angiogenesis

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