Controlled hypobaric hypoxia increases immunological tolerance by modifying HLA-G expression, a potential therapy to inflammatory diseases

Ziliotto, Marina; Rodrigues, Raul Marques

doi:10.1016/j.mehy.2020.109664

Cited by 8 publications

(3 citation statements)

References 37 publications

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“…From a clinical standpoint, hypobaric chambers can control chronic inflammation in several inflammatory conditions, including autoimmune/autoinflammatory diseases and systemic inflammation in HIV-infected subjects on antiretroviral treatment (ART). Induction of hypoxia is an effective immunotolerogenic inducer in subjects with HIV infection [ 83 ].…”

Section: Resultsmentioning

confidence: 99%

Immunological Response to Exercise in Athletes with Disabilities: A Narrative Review of the Literature

2023

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For a person with a disability, participating in sports activities and/or competitions can be a challenge for the immune system. The relationship between exercise and immunity response in disabled athletes is, indeed, extremely complex for several reasons, including (1) the chronic low-grade inflammatory and immunodepression—“secondary immune deficiency”—state imposed by the disability/impairment; (2) the impact of the disability on an array of variables, spanning from physical fitness to well-being, quality of life, sleep, and nutritional aspects, among others, which are known to mediate/modulate the effects of exercise on human health; (3) the variability of the parameters related to the exercise/physical activity (modality, frequency, intensity, duration, training versus competition, etc.); and (4) the intra- and inter-individual variability of the immunological response to exercise. In able-bodied athletes, previously published data described several exercise-induced changes affecting various immunological subsets and subpopulations, ranging from neutrophils to lymphocytes, and monocytes. Broadly, moderate intensity workout is accompanied by optimal immunity and resistance to infections such as upper respiratory tract infections (URTI) in athletes. Periods of intense training with insufficient recovery can cause a temporary state of immunosuppression, which should end with a few days of rest/recovery from exercise. Disabled athletes are relatively overlooked and understudied with respect to their able-bodied counterparts. Findings from the few studies available on paralympic and disabled athletes are here summarized and analyzed utilizing a narrative approach to review and determine the major features of the immunological and inflammatory responses to exercise in this specific population. Moreover, a few studies have reported behavioral, dietary, and training strategies that can be adopted to limit exercise-induced immunosuppression and reduce the risk of infection in people with disabilities. However, given the paucity of data and contrasting findings, future high-quality investigations on paralympic and disabled athletes are urgently needed.

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Section: Resultsmentioning

confidence: 99%

Immunological Response to Exercise in Athletes with Disabilities: A Narrative Review of the Literature

2023

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“…Moreover, mechanisms involved in regulation of HLA-G expression are complex. In addition to the HLA-G genetic variations both in 5′upstream regulatory region and in 3′-untranslated region which comprise binding sites for transcription factor and microRNAs and epigenetic modifications (32), other environmental factor such as hypoxia, cytokines, hormones, and even immunotherapy chemicals and radiation have been acknowledged to be related to the regulation of HLA-G expression (33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

Intratumor Heterogeneity of HLA-G Expression in Cancer Lesions

et al. 2020

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Signaling pathway between human leukocyte antigen (HLA)-G and immune inhibitory receptors immunoglobulin-like transcript (ILT)-2/4 has been acknowledged as one of immune checkpoints, and as a potential target for cancer immunotherapy. Like other immune checkpoints, inter-and even intratumor heterogeneity of HLA-G could render a rather complexity for HLA-G-target immunotherapy. However, little information for intratumor heterogeneity of HLA-G is available. In this study, HLA-G expression in a serial section of colorectal cancer (CRC) lesions from three CRC patients (each sample with serial section of 50 slides, 10 randomized slides for each antibody), three different locations within a same sample (five CRC), and three case-matched blocks that each includes 36 esophageal cancer samples, were evaluated with immunohistochemistry using anti-HLA-G antibodies (mAbs 4H84, MEM-G/1 and MEM-G/2 probing for all denatured HLA-G isoforms, 5A6G7, and 2A12 probing for denatured HLA-G5 and HLA-G6 isoforms). Our results revealed that, in addition to the frequently observed inter-tumor heterogeneity, intratumor heterogeneous expression of HLA-G is common in different areas within a tumor in CRC and esophageal cancer samples included in this study. Moreover, percentage of HLA-G expression probed with different anti-HLA-G antibodies also varies dramatically within a tumor. Given HLA-G has been considered as an important immune checkpoint, intratumor heterogeneity of HLA-G expression, and different specificity of anti-HLA-G antibodies being used among studies, interpretation and clinical significance of HLA-G expression in cancers should be with caution.

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“…It might be explained by the fact, that the levels of sHLA-G in glioma patients are influenced not only by HLA-G variants, but also by environmental factors, such as treatment, hormones, stress, and hypoxia[69,70]. However, Magalhaes et al (2020) found an association of the of the heterozygous 14 bp ins/del and +3142 C/G genotypes of the HLA-G 3' UTR with higher HLA-G plasma levels in grade IV glioma patients when compared with controls[61].Comparing plasma levels of sHLA-G in our group of patients with methylated and unmethylated MGMT (methylguanidine methyltransferase) promoter, patients with methylated MGMT promoter were shown to have lower plasma levels of the immunosuppressive molecule sHLA-G than those with unmethylated MGMT promoter.…”

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confidence: 99%

HLA-G 14bp ins/del Polymorphism, Plasma Level of Soluble HLA-G and Association with IL-6/IL-10 Ratio and Survival of Glioma Patients

Bucová¹,

Klučková²,

Kozák³

et al. 2021

Preprint

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HLA-G is an immune checkpoint molecule with immunosuppressive and anti-inflammatory activities, and its expression and level of its soluble form (sHLA-G) may play an important role in tumor prognosis. The HLA-G 14 bp ins/del polymorphism and the plasma level of soluble HLA-G (sHLA-G) were investigated by a polymerase chain reaction and ELISA, respectively, in 59 glioma patients. A significantly higher proportion of glioma patients had the 14 nt insert in both homozygous and heterozygous states compared to the control group. Glioma patients had also higher plasma levels of sHLA-G. Patients with methylated MGMT promoter had lower levels of sHLA-G than those with unmethylated MGMT promoter. Level of sHLA-G negatively correlated with the overall survival of patients. Glioblastoma patients who survived more than one year after diagnosis had lower levels of sHLA-G than those surviving less than one year. Patients with sHLA-G levels below the cut off value 40 U/mL survived significantly longer than patients with sHLA-G above 40 U/mL. The levels of sHLA-G also negatively correlated with the level of IL-6 (P=0.0004) and positively with IL-10/IL-6 (P=0.046). Conclusion: The presence of 14 nt insert in both homozygous and heterozygous states of the HLA-G 14 bp ins/del polymorphism is more frequent in glioma patients and the elevated plasma levels of sHLA-G are negatively associated with their survival.

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Controlled hypobaric hypoxia increases immunological tolerance by modifying HLA-G expression, a potential therapy to inflammatory diseases

Cited by 8 publications

References 37 publications

Immunological Response to Exercise in Athletes with Disabilities: A Narrative Review of the Literature

Immunological Response to Exercise in Athletes with Disabilities: A Narrative Review of the Literature

Intratumor Heterogeneity of HLA-G Expression in Cancer Lesions

HLA-G 14bp ins/del Polymorphism, Plasma Level of Soluble HLA-G and Association with IL-6/IL-10 Ratio and Survival of Glioma Patients

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