Targeting Opposing Immunological Roles of the Junctional Adhesion Molecule-A in Autoimmunity and Cancer

Bonilha, Caio S.; Benson, Robert A.; Brewer, James M.; Garside, Paul

doi:10.3389/fimmu.2020.602094

Cited by 16 publications

(9 citation statements)

References 75 publications

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“…JAMs are intercellular adhesion molecules that importantly participate in the transmigration of monocytes, neutrophils, and some T cells through homophilic and heterophilic interactions [ 22 ]. Increasing evidence suggests that JAM family members could have potential clinical relevance in cancer development and function as tumor suppressors [ 23 , 24 ]. JAML has been reported as a new JAM family member, and its role in LUAD has not yet been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Junctional Adhesion Molecule-Like Protein (JAML) Is Correlated with Prognosis and Immune Infiltrates in Lung Adenocarcinoma

Fang

et al. 2021

Med Sci Monit

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Background Junctional adhesion molecule-like protein (JAML) is a member of the junctional adhesion molecule family and mediates migration of immune cells, but its function in cancers remains unclear. This study aimed to evaluate the role of JAML in the prognosis and immune infiltrates of lung adenocarcinoma (LUAD). Material/Methods JAML expressions in LUAD tissues and normal tissues were compared using The Cancer Genome Atlas (TCGA) database and datasets from the Gene Expression Omnibus (GEO) database. The influence of JAML expression on prognosis was analyzed by Kaplan-Meier curve and Cox regression model. Interactive and functional analyses of JAML were performed by LinkedOmics and GeneMANIA databases. TIMER2.0, TISIDB, and GEPIA2 databases were used to investigate the correlation between JAML expression and immune infiltrates. Results JAML expression was decreased in LUAD ( P <0.001), and lower JAML expression was associated with worse outcomes of LUAD patients. High JAML expression was the protective factor for overall survival (OS) (HR 0.706, 95% CI 0.500–0.997, P =0.048). Interactive and functional analyses suggested that co-expressed genes with JAML have an obvious link to immune-related pathways. In addition, JAML expression was positively associated with infiltrating levels of CD8+ T cells, CD4+ T cells, B cells, dendritic cells, macrophages, and neutrophils, and had significant correlations with diverse immune marker sets in LUAD. Conclusions JAML expression was significantly correlated with prognosis and immune infiltrates. These preliminary findings suggested JAML could be considered as a potential prognostic biomarker and therapeutic target for LUAD.

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Section: Discussionmentioning

confidence: 99%

Junctional Adhesion Molecule-Like Protein (JAML) Is Correlated with Prognosis and Immune Infiltrates in Lung Adenocarcinoma

Fang

et al. 2021

Med Sci Monit

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“…Based on the critical role the adaptive immune system plays in controlling infection in sepsis and modulating the host inflammatory response (43,44), we examined the role of JAM-A on lymphocytes in sepsis. Previous studies demonstrate that treatment with either anti-JAM-A antibody or JAM-A-Fc fusion protein inhibits migration of human memory CD4 + T cells (45).…”

Section: Discussionmentioning

confidence: 99%

Junctional adhesion molecule-A deletion increases phagocytosis and improves survival in a murine model of sepsis

Klingensmith¹,

Fay²,

Swift³

et al. 2022

JCI Insight

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The tight junction-associated protein Junctional Adhesion Molecule-A (JAM-A) is increased in sepsis although the significance of this is unknown. Here we show that septic JAM-A -/mice have increased gut permeability. Paradoxically, septic JAM-A -/mice have decreased bacteremia and systemic TNF and IL-1β. Survival is improved in JAM-A -/mice. However intestine-specific JAM-A -/deletion does not alter mortality suggesting the mortality benefit conferred in mice lacking JAM-A is independent of the intestine. Septic JAM-A -/mice have increased splenic CD44 hi CD4 + T cells with decreased frequency of TNF + CD4 + cells and elevated frequency of IL-2 + CD4 + cells. Septic JAM-A -/mice have increased B cells in mesenteric lymph nodes with elevated serum IgA and intraepithelial lymphocyte IgA production. JAM-A -/x RAG -/mice have improved survival compared to RAG -/mice and identical mortality as WT mice.Gut neutrophil infiltration is increased in JAM-A -/mice and neutrophil phagocytosis is increased. Septic JAM-A -/mice depleted of neutrophils lose their survival advantage. Therefore increased bacterial clearance via neutrophils and an altered systemic inflammatory response with increased opsonizing IgA produced through the adaptive immune system results in improved survival in septic JAM-A -/mice. JAM-A may be a therapeutic target in sepsis via immune mechanisms not related to its role in permeability.

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“…In vitro blockade inhibits the transmigration of monocytes, neutrophils and T cells, while JAM-A deficiency in mice has been shown to increase DC trafficking to LNs and to increase contact hypersensitivity responses (28). JAM-A has been shown to play complex roles in a variety of inflammatory conditions reviewed in Bonilha et al (29). F11r was reported to be upregulated in PMBCs of RA patients (30).…”

Section: Discussionmentioning

confidence: 99%

Dissecting the molecular control of immune cell accumulation in the inflamed joint

Prendergast¹,

Benson²,

Scales³

et al. 2022

JCI Insight

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Mechanisms governing entry and exit of immune cells into, and out of, inflamed joints, remain poorly understood. We sought herein to identify the key molecular pathways regulating such migration. Using murine models of inflammation in conjunction with mice expressing a photoconvertible fluorescent protein we characterized the migration of cells from joints to draining lymph nodes (LN) and performed RNA-seq analysis on isolated cells, identifying genes associated with migration and retention. We further refined the gene list to those specific for joint inflammation. RNA-seq data revealed pathways and genes previously highlighted as characteristic of Rheumatoid arthritis (RA) in patient studies, validating the methodology.Focusing on pathways associated with cell migration, adhesion and movement, we identified genes involved in the retention of immune cells in the inflamed joint, namely JAM-A, and identified a role for such molecules in T cell differentiation in vivo.Thus, using a combination of novel cell tracking approaches and murine models of inflammatory arthritis we have identified genes, pathways and anatomically specific tissue signatures regulating cell migration in a variety of inflamed sites. This unique skin and joint specific dataset will be an invaluable resource for the identification of novel therapeutic targets for arthritis and other inflammatory disorders.

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Targeting Opposing Immunological Roles of the Junctional Adhesion Molecule-A in Autoimmunity and Cancer

Cited by 16 publications

References 75 publications

Junctional Adhesion Molecule-Like Protein (JAML) Is Correlated with Prognosis and Immune Infiltrates in Lung Adenocarcinoma

Junctional Adhesion Molecule-Like Protein (JAML) Is Correlated with Prognosis and Immune Infiltrates in Lung Adenocarcinoma

Junctional adhesion molecule-A deletion increases phagocytosis and improves survival in a murine model of sepsis

Dissecting the molecular control of immune cell accumulation in the inflamed joint

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