Lymphocyte Trafficking

Kogan, Avi N; Andrian, Ulrich H. von

doi:10.1002/cphy.cp020410

Cited by 4 publications

(3 citation statements)

References 321 publications

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“…Because in MS patients, trafficking through non-BBB endothelial cells probably takes place in more physiological conditions, we performed the transmigration assay with non-activated BECs and LECs, thus avoiding the addition of any exogenous cytokine (exception made for the VEGF used for cell growth) that would make results difficult to be interpreted. In this setting, the transmigration is mediated only by the interaction of integrins present on lymphocyte surface with their ligands on endothelial cells [30]. In these experimental conditions, using all the appropriate controls, we demonstrated that natalizumab therapy only marginally interferes with the ability of T and B lymphocytes to pass through non-activated monolayers of BECs and LECs.…”

Section: Discussionmentioning

confidence: 82%

Peripheral accumulation of newly produced T and B lymphocytes in natalizumab-treated multiple sclerosis patients

Zanotti

Chiarini

Serana

et al. 2012

Clinical Immunology

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The anti-α4 monoclonal antibody natalizumab inhibits lymphocyte extravasation into the central nervous system and increases peripheral T and B lymphocytes in multiple sclerosis patients. To investigate whether the lymphocyte accumulation was due to a higher lymphocyte production, an altered homeostasis, or a differential transmigration of lymphocyte subsets through endothelia, T-cell receptor excision circles and kappa-deleting recombination excision circles were quantified before and after treatment, T-cell receptor repertoire was analyzed by spectratyping, and T-and B-lymphocyte subset migration was studied using transwell coated with vascular and lymphatic endothelial cells. We found that the number of newly produced T and B lymphocytes is increased because of a high release and of a low propensity of naïve subsets to migrate across endothelial cells. In some patients this resulted in an enlargement of T-cell heterogeneity. Because new lymphocyte production ensures the integrity of immune surveillance, its quantification could be used to monitor natalizumab therapy safety.

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Section: Discussionmentioning

confidence: 82%

Peripheral accumulation of newly produced T and B lymphocytes in natalizumab-treated multiple sclerosis patients

Zanotti

Chiarini

Serana

et al. 2012

Clinical Immunology

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“…Aquaporins facilitate cell migration by mediating water influx into membrane protrusions, which causes actin reorganization and the formation of lamellipodia, which provides a foundation for the cell to move forward [ 26 ]. Neutrophil cells and macrophages, derived from monocytes, are most prominent to migrate into tissue via lamellipodia formation [ 27 , 28 , 29 ], whereas this mechanism is not predominantly described in lymphocytes [ 30 ]. As a former study demonstrated the role of promoter methylation in inflammatory cells in lung-disease [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

AQP5-1364A/C Polymorphism Affects AQP5 Promoter Methylation

Rump

Spellenberg

Busch

et al. 2022

IJMS

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The quantity of aquaporin 5 protein in neutrophil granulocytes is associated with human sepsis-survival. The C-allele of the aquaporin (AQP5)-1364A/C polymorphism was shown to be associated with decreased AQP5 expression, which was shown to be relevant in this context leading towards improved outcomes in sepsis. To date, the underlying mechanism of the C-allele—leading to lower AQP5 expression—has been unknown. Knowing the detailed mechanism depicts a crucial step with a target to further interventions. Genotype-dependent regulation of AQP5 expression might be mediated by the epigenetic mechanism of promoter methylation and treatment with epigenetic-drugs could maybe provide benefit. Hence, we tested the hypothesis that AQP5 promoter methylation differs between genotypes in specific types of immune cells.: AQP5 promoter methylation was quantified in cells of septic patients and controls by methylation-specific polymerase chain reaction and quantified by a standard curve. In cell-line models, AQP5 expression was analyzed after demethylation to determine the impact of promoter methylation on AQP5 expression. C-allele of AQP5-1364 A/C promoter polymorphism is associated with a five-fold increased promoter methylation in neutrophils (p = 0.0055) and a four-fold increase in monocytes (p = 0.0005) and lymphocytes (p = 0.0184) in septic patients and healthy controls as well. In addition, a decreased AQP5 promoter methylation was accompanied by an increased AQP5 expression in HL-60 (p = 0.0102) and REH cells (p = 0.0102). The C-allele which is associated with lower gene expression in sepsis is accompanied by a higher methylation level of the AQP5 promoter. Hence, AQP5 promoter methylation could depict a key mechanism in genotype-dependent expression.

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“…Принципиально иное решение проблемы предлагают ГИБП, ингибирующие интегрины. В норме контролируемая миграция Т-лимфоцитов в слизистую оболочку кишечника играет ключевую роль в иммунном надзоре здорового кишечника [24,27,28]. Усиленная миграция патогенных Т-лимфоцитов признана наиболее важным механизмом в патогенезе ВЗК и поддержании порочного круга высвобождения провоспалительных цитокинов в собственной пластинке слизистой оболочки кишечника [25,26,[29][30][31].…”

Section: локализация противовоспалительного эффекта имеет значениеunclassified

Immunological aspects of determination of an adequate biological treatment sequence for inflammatory bowel diseases: the expert board statement (St. Petersburg, May 22, 2021)

Белоусова

Kozlov²,

Абдулганиева

et al. 2021

Alʹm. klin. med.

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On May 22, 2021, the Expert Board met in St. Petersburg to discuss their position on immunological aspects of determination of an adequate biological treatment sequence for inflammatory bowel diseases (IBD). The Expert Board aimed at discussion of current strategies, development of a consensus on determination of an adequate biological treatment sequence for IBD. The main topics of the agenda were the contribution of immune system to the pathophysiology of Crohn's disease, ulcerative colitis and their complications, efficacy of genetically engineered biological agents (GEBA) at various stages of IBD management. Participation of the leading Russian experts in IBD, as well as involvement of other specialties, made it possible to consider the topic by a multidisciplinary team, with an in-depth analysis of IBD pathophysiology, to better understand the course of the disease in some contradictory situation, for instance, when clinical remission is not associated with an endoscopically confirmed remission. One of the expected effects of this Expert Board meeting would be an improvement of GEBA administration in clinical practice, mostly due to the modification of clinical guidelines. This would ascertain and confirm the algorithms for GEBA administration for IBD, including the optimal treatment sequence depending on an agent’s mechanism of action and the patient profile. The clarification of the optimal GEBA sequence in the clinical guidelines could lead to more frequent GEBA administration in local medical clinics and institutions in the regions, where GEBA are used insufficiently due to little experience and absence of their precise positioning in the clinical guidelines.

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Lymphocyte Trafficking

Cited by 4 publications

References 321 publications

Peripheral accumulation of newly produced T and B lymphocytes in natalizumab-treated multiple sclerosis patients

Peripheral accumulation of newly produced T and B lymphocytes in natalizumab-treated multiple sclerosis patients

AQP5-1364A/C Polymorphism Affects AQP5 Promoter Methylation

Immunological aspects of determination of an adequate biological treatment sequence for inflammatory bowel diseases: the expert board statement (St. Petersburg, May 22, 2021)

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