JAML mediates monocyte and CD8 T cell migration across the brain endothelium

Alvarez, Jorge Iván; Kébir, Hania; Cheslow, Lara; Chabarati, Marc; Larochelle, Catherine; Prat, Alexandre

doi:10.1002/acn3.255

Cited by 40 publications

(27 citation statements)

References 18 publications

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“…Further, BTN3 genes have been associated with T1D in a genetic screen, especially in the case of BTN3A2 (54). AMICA1 is a plasma membrane protein involved in lymphocyte migration through its interaction with Coxsackie-adenovirus receptor (CAR) expressed in epithelial cells and has been associated with multiple sclerosis (55). An analogous scenario could be envisaged for T1D: CAR is expressed by the pancreatic islet cells, including b-cells (42), and its expression is elevated in autoantibody-positive individuals and patients with T1D (56), suggesting that it might help recruit T cells to the islets.…”

Section: Discussionmentioning

confidence: 99%

Early Detection of Peripheral Blood Cell Signature in Children Developing β-Cell Autoimmunity at a Young Age

et al. 2019

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The appearance of type 1 diabetes (T1D)-associated autoantibodies is the first and only measurable parameter to predict progression toward T1D in genetically susceptible individuals. However, autoantibodies indicate an active autoimmune reaction, wherein the immune tolerance is already broken. Therefore, there is a clear and urgent need for new biomarkers that predict the onset of the autoimmune reaction preceding autoantibody positivity or reflect progressive β-cell destruction. Here we report the mRNA sequencing–based analysis of 306 samples including fractionated samples of CD4+ and CD8+ T cells as well as CD4−CD8− cell fractions and unfractionated peripheral blood mononuclear cell samples longitudinally collected from seven children who developed β-cell autoimmunity (case subjects) at a young age and matched control subjects. We identified transcripts, including interleukin 32 (IL32), that were upregulated before T1D-associated autoantibodies appeared. Single-cell RNA sequencing studies revealed that high IL32 in case samples was contributed mainly by activated T cells and NK cells. Further, we showed that IL32 expression can be induced by a virus and cytokines in pancreatic islets and β-cells, respectively. The results provide a basis for early detection of aberrations in the immune system function before T1D and suggest a potential role for IL32 in the pathogenesis of T1D.

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Section: Discussionmentioning

confidence: 99%

Early Detection of Peripheral Blood Cell Signature in Children Developing β-Cell Autoimmunity at a Young Age

et al. 2019

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“…This could enable targeting pathological inflammation without rendering patients more vulnerable to infection. Indeed, ninjurin1 (NINJ1; monocytes), activated leukocyte cell adhesion molecule (ALCAM; CD4 + T cells, monocytes), junction adhesion molecule–like (JAML; monocytes, CD8 + T cells), and melanoma cell adhesion molecule (MCAM; CD8, T helper cell 17) regulate the entry of specific immune cell populations into the CNS (Alvarez et al, 2015; Cayrol et al, 2008; Flanagan et al, 2012; Ifergan et al, 2011; Larochelle et al, 2015). It will be necessary to ensure that targeting these molecules does not produce secondary effects; Alcam knockout mice develop more severe EAE as ALCAM also enforces TJ integrity (Lécuyer et al, 2017).…”

Section: Bbb Dysfunctionmentioning

confidence: 99%

The blood–brain barrier in health and disease: Important unanswered questions

Profaci

Munji

Pulido

et al. 2020

Journal of Experimental Medicine

471

358

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The blood vessels vascularizing the central nervous system exhibit a series of distinct properties that tightly control the movement of ions, molecules, and cells between the blood and the parenchyma. This “blood–brain barrier” is initiated during angiogenesis via signals from the surrounding neural environment, and its integrity remains vital for homeostasis and neural protection throughout life. Blood–brain barrier dysfunction contributes to pathology in a range of neurological conditions including multiple sclerosis, stroke, and epilepsy, and has also been implicated in neurodegenerative diseases such as Alzheimer’s disease. This review will discuss current knowledge and key unanswered questions regarding the blood–brain barrier in health and disease.

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“…4 Among the molecules involved in neutrophil adhesion functions, the hematopoietic progenitor kinase 1 gene (Hpk1 alias Map4k1) 23 was upregulated in HS rats as well as Jam2, a junctional adhesion molecule implicated in leukocyte migration. 24 Amica1 (alias Jaml) however, a transmembrane protein involved in leukocyte transendothelial migration 25 and T-cell costimulation, 26 was downregulated in HS rats, demonstrating that within the same functional process (leukocyte adhesion and migration) different molecules can be specifically regulated. In HS, we observed the downregulation of genes involved in the adaptive immune response: the immunoglobulin genes Cd79b and Ighm, genes of the rat major histocompatibility complex (RT1-Ba, RT1-Da, RT1-Db1, RT1-N3), Ms4a1 encoding a transmembrane protein, selectively expressed on mature B cells.…”

Section: Discussionmentioning

confidence: 99%

Preliminary profiling of blood transcriptome in a rat model of hemorrhagic shock

Braga

Barcella

D’Avila

et al. 2017

Exp Biol Med (Maywood)

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Hemorrhagic shock is a leading cause of morbidity and mortality worldwide. Significant blood loss may lead to decreased blood pressure and inadequate tissue perfusion with resultant organ failure and death, even after replacement of lost blood volume. One reason for this high acuity is that the fundamental mechanisms of shock are poorly understood. Proteomic and metabolomic approaches have been used to investigate the molecular events occurring in hemorrhagic shock but, to our knowledge, a systematic analysis of the transcriptomic profile is missing. Therefore, a pilot analysis using paired-end RNA sequencing was used to identify changes that occur in the blood transcriptome of rats subjected to hemorrhagic shock after blood reinfusion. Hemorrhagic shock was induced using a Wigger's shock model. The transcriptome of whole blood from shocked animals shows modulation of genes related to inflammation and immune response (Tlr13, Il1b, Ccl6, Lgals3), antioxidant functions (Mt2A, Mt1), tissue injury and repair pathways (Gpnmb, Trim72) and lipid mediators (Alox5ap, Ltb4r, Ptger2) compared with control animals. These findings are congruent with results obtained in hemorrhagic shock analysis by other authors using metabolomics and proteomics. The analysis of blood transcriptome may be a valuable tool to understand the biological changes occurring in hemorrhagic shock and a promising approach for the identification of novel biomarkers and therapeutic targets. Impact statement This study provides the first pilot analysis of the changes occurring in transcriptome expression of whole blood in hemorrhagic shock (HS) rats. We showed that the analysis of blood transcriptome is a useful approach to investigate pathways and functional alterations in this disease condition. This pilot study encourages the possible application of transcriptome analysis in the clinical setting, for the molecular profiling of whole blood in HS patients.

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JAML mediates monocyte and CD8 T cell migration across the brain endothelium

Cited by 40 publications

References 18 publications

Early Detection of Peripheral Blood Cell Signature in Children Developing β-Cell Autoimmunity at a Young Age

Early Detection of Peripheral Blood Cell Signature in Children Developing β-Cell Autoimmunity at a Young Age

The blood–brain barrier in health and disease: Important unanswered questions

Preliminary profiling of blood transcriptome in a rat model of hemorrhagic shock

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