Role of Exercise Intensity on Th1/Th2 Immune Modulations During the COVID-19 Pandemic

The COVID-19 pandemic has led to several pioneering scientific discoveries resulting in no effective solutions with the exception of vaccination. Moderate exercise is a significant non-pharmacological strategy, to reduce the infection-related burden of COVID-19, especially in patients who are obese, elderly, and with additional comorbidities. The imbalance of T helper type 1 (Th1) or T helper type 2 (Th2) cells has been well documented among populations who have suffered as a result of the COVID-19 pandemic, and who are at maximum risk of infection and mortality. Moderate and low intensity exercise can benefit persons at risk from the disease and survivors by favorable modulation in Th1/Th2 ratios. Moreover, in COVID-19 patients, mild to moderate intensity aerobic exercise also increases immune system function but high intensity aerobic exercise may have adverse effects on immune responses. In addition, sustained hypoxia in COVID-19 patients has been reported to cause organ failure and cell death. Hypoxic conditions have also been highlighted to be triggered in COVID-19-susceptible individuals and COVID-19 survivors. This suggests that hypoxia inducible factor (HIF 1α) might be an important focus for researchers investigating effective strategies to minimize the effects of the pandemic. Intermittent hypoxic preconditioning (IHP) is a method of exposing subjects to short bouts of moderate hypoxia interspersed with brief periods of normal oxygen concentrations (recovery). This methodology inhibits the production of pro-inflammatory factors, activates HIF-1α to activate target genes, and subsequently leads to a higher production of red blood cells and hemoglobin. This increases angiogenesis and increases oxygen transport capacity. These factors can help alleviate virus induced cardiopulmonary hemodynamic disorders and endothelial dysfunction. Therefore, during the COVID-19 pandemic we propose that populations should engage in low to moderate exercise individually designed, prescribed and specific, that utilizes IHP including pranayama (yoga), swimming and high-altitude hiking exercise. This would be beneficial in affecting HIF-1α to combat the disease and its severity. Therefore, the promotion of certain exercises should be considered by all sections of the population. However, exercise recommendations and prescription for COVID-19 patients should be structured to match individual levels of capability and adaptability.

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The roles of immune cells in atherosclerotic calcification

Vascular ◽

10.1177/17085381211032756 ◽

2021 ◽

pp. 170853812110327

Author(s):

Jingsong Cao ◽

Xuyu Zu ◽

Jianghua Liu

Keyword(s):

B Cells ◽

Immune Cells ◽

Cardiovascular Events ◽

Th2 Cells ◽

Regulatory B Cells ◽

T Helper ◽

Relationship Of ◽

The Relationship ◽

Helper Type

Atherosclerosis is the leading cause of acute cardiovascular events, and vascular calcification is an important pathological phenomenon in atherosclerosis. Recently, many studies have shown that immune cells are closely associated with the development of atherosclerosis and calcification, but there are many conflicting viewpoints because of immune system complications, such as the pro-atherosclerotic and atheroprotective effects of regulatory B cells (Bregs), T helper type 2 (Th2) cells and T helper type 17 (Th17) cells. In this review, we summarize the studies on the roles of immune cells, especially lymphocytes and macrophages, in atherosclerotic calcification. Furthermore, we prepared graphs showing the relationship between T cells, B cells and macrophages and atherosclerotic calcification. Finally, we highlight some potential issues that are closely associated with the function of immune cells in atherosclerotic calcification. Based on current research results, this review summarizes the relationship between immune cells and atherosclerotic calcification, and it will be beneficial to understand the relationship of immune cells and atherosclerotic calcification.

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Critical Involvement of CD44 in T Helper Type 2 Cell-Mediated Eosinophilic Airway Inflammation in a Mouse Model of Acute Asthma

Frontiers in Immunology ◽

10.3389/fimmu.2021.811600 ◽

2022 ◽

Vol 12 ◽

Author(s):

Shigeki Katoh

Keyword(s):

Monoclonal Antibodies ◽

Airway Inflammation ◽

Th17 Cells ◽

Acute Asthma ◽

Mite Allergen ◽

Th2 Cells ◽

T Helper ◽

Th2 Cell ◽

Helper Type

Interactions between CD44 and hyaluronan (HA) are crucial for recruiting leukocytes to inflamed tissues. This review summarizes findings from our studies of the roles of CD44-HA interactions in leukocyte trafficking, with a particular focus on airway T helper type 2 (Th2) cells in mouse models of acute asthma. In a mite allergen-induced model of acute asthma, intraperitoneal injection of anti-CD44 monoclonal antibodies blocked lymphocytes and eosinophils from accumulating in the lung, and suppressed both the antigen-induced increase in Th2 cytokines in the bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness (AHR). CD44 deficiency was associated with decreased mite allergen-induced Th2 cell-mediated airway inflammation and AHR in sensitized mice. Asthmatic responses to antigen-sensitized splenic CD4+ T cells transferred from CD44-deficient mice were weaker than in wild-type mice. Administration of anti-CD44 monoclonal antibodies preferentially suppressed the airway accumulation of antigen-specific Th2 cells induced by antigen challenge, without affecting Th1 and Th17 cells. Increased HA-binding ability of CD44 and expression of Neu1 sialidase were observed on antigen-specific Th2 cells compared with antigen-specific Th1 and Th17 cells. Finally, in a mouse model of acute asthma, neuraminidase 1-deficient SM/J mice exhibited a lower Th2 cytokine concentration and a lower absolute Th2 cell number in the BALF, as well as an attenuated AHR. Our findings indicate that CD44 critically contributes to the antigen challenge-induced airway accumulation of antigen-specific Th2 cells, without affecting Th1 and Th17 cells, in mice. Furthermore, neuraminidase 1 activity is necessary for the interaction between HA and CD44, and Th2 cell-mediated airway inflammation.

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A dominant role for chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cells (CRTH2) in mediating chemotaxis of CRTH2+ CD4+Th2 lymphocytes in response to mast cell supernatants

Immunology ◽

10.1111/j.1365-2567.2006.02440.x ◽

2006 ◽

Vol 119 (3) ◽

pp. 362-368 ◽

Cited By ~ 37

Author(s):

Shân L. Gyles ◽

Luzheng Xue ◽

Elizabeth R. Townsend ◽

Frank Wettey ◽

Roy Pettipher

Keyword(s):

Mast Cell ◽

Dominant Role ◽

Th2 Cells ◽

T Helper ◽

Helper Type

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A critical role for transforming growth factor-beta but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RB(low) CD4+ T cells.

Journal of Experimental Medicine ◽

10.1084/jem.183.6.2669 ◽

1996 ◽

Vol 183 (6) ◽

pp. 2669-2674 ◽

Cited By ~ 654

Author(s):

F Powrie ◽

J Carlino ◽

M W Leach ◽

S Mauze ◽

R L Coffman

Keyword(s):

T Cells ◽

Growth Factor ◽

Cd4 T Cells ◽

Transforming Growth Factor ◽

Th2 Cells ◽

Tgf Beta ◽

T Helper ◽

Cd4 Cells ◽

Helper Type

A T helper type 1 (Th1)-mediated colitis with similarities to inflammatory bowel disease in humans developed in severe combined immunodeficiency mice reconstituted with CD45RB(high) CD4+ splenic T cells and could be prevented by cotransfer of CD45RB(low) CD4+ T cells. Inhibition of this Th1 response by the CD45RB(low) T cell population could be reversed in vivo by an anti-transforming growth factor (TGF) beta antibody. Interleukin (IL) 4 was not required for either the differentiation of function of protective cells as CD45RB(low) CD4+ cells from IL-4-deficient mice were fully effective. These results identify a subpopulation of peripheral CD4+ cells and TGF-beta as critical components of the natural immune regulatory mechanism, which prevents the development of pathogenic Th1 responses in the gut, and suggests that this immunoregulatory population is distinct from Th2 cells.

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Prostaglandin D2 Selectively Induces Chemotaxis in T Helper Type 2 Cells, Eosinophils, and Basophils via Seven-Transmembrane Receptor Crth2

Journal of Experimental Medicine ◽

10.1084/jem.193.2.255 ◽

2001 ◽

Vol 193 (2) ◽

pp. 255-262 ◽

Cited By ~ 765

Author(s):

Hiroyuki Hirai ◽

Kazuya Tanaka ◽

Osamu Yoshie ◽

Kazuyuki Ogawa ◽

Kazumi Kenmotsu ◽

...

Keyword(s):

Allergic Inflammation ◽

Allergic Diseases ◽

Th2 Cells ◽

Prostaglandin D2 ◽

Dependent Manner ◽

T Helper ◽

Dependent Cell ◽

Blood Eosinophils ◽

Helper Type

Prostaglandin (PG)D2, which has long been implicated in allergic diseases, is currently considered to elicit its biological actions through the DP receptor (DP). Involvement of DP in the formation of allergic asthma was recently demonstrated with DP-deficient mice. However, proinflammatory functions of PGD2 cannot be explained by DP alone. We show here that a seven-transmembrane receptor, CRTH2, which is preferentially expressed in T helper type 2 (Th2) cells, eosinophils, and basophils in humans, serves as the novel receptor for PGD2. In response to PGD2, CRTH2 induces intracellular Ca2+ mobilization and chemotaxis in Th2 cells in a Gαi-dependent manner. In addition, CRTH2, but not DP, mediates PGD2-dependent cell migration of blood eosinophils and basophils. Thus, PGD2 is likely involved in multiple aspects of allergic inflammation through its dual receptor systems, DP and CRTH2.

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Regulation of T helper type 2 cell differentiation by murine Schnurri-2

Journal of Experimental Medicine ◽

10.1084/jem.20040733 ◽

2005 ◽

Vol 201 (3) ◽

pp. 397-408 ◽

Cited By ~ 42

Author(s):

Motoko Y. Kimura ◽

Hiroyuki Hosokawa ◽

Masakatsu Yamashita ◽

Akihiro Hasegawa ◽

Chiaki Iwamura ◽

...

Keyword(s):

Cell Differentiation ◽

Transforming Growth Factor ◽

Zinc Finger Protein ◽

Transforming Growth Factor Β ◽

Cell Receptor ◽

Th2 Cells ◽

Marginal Effect ◽

T Helper ◽

Th1 Cell ◽

Helper Type

Schnurri (Shn) is a large zinc finger protein implicated in cell growth, signal transduction, and lymphocyte development. Vertebrates possess at least three Shn orthologues (Shn-1, Shn-2, and Shn-3), which appear to act within the bone morphogenetic protein, transforming growth factor β, and activin signaling pathways. However, the physiological functions of the Shn proteins remain largely unknown. In Shn-2–deficient mice, mature peripheral T cells exhibited normal anti–T cell receptor–induced proliferation, although there was dramatic enhancement in the differentiation into T helper type (Th)2 cells and a marginal effect on Th1 cell differentiation. Shn-2–deficient developing Th2 cells showed constitutive activation of nuclear factor κB (NF-κB) and enhanced GATA3 induction. Shn-2 was able to compete with p50 NF-κB for binding to a consensus NF-κB motif and inhibit NF-κB–driven promoter activity. Thus, Shn-2 plays a crucial role in the control of Th2 cell differentiation by regulating NF-κB function.

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IFN-α Destabilizes Human CD4+ T Helper Type 2 (Th2) Cells By Disrupting the Th2-Specific Transcription Program

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2012.01.002 ◽

2012 ◽

Vol 129 (2) ◽

pp. AB364

Author(s):

J. Huber ◽

J. Farrar

Keyword(s):

Th2 Cells ◽

T Helper ◽

Transcription Program ◽

Helper Type

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Investigation of interleukin 10, 12 and 18 levels in patients with head and neck cancer

The Journal of Laryngology & Otology ◽

10.1017/s0022215106002428 ◽

2006 ◽

Vol 121 (3) ◽

pp. 246-252 ◽

Cited By ~ 48

Author(s):

A Jebreel ◽

D Mistry ◽

D Loke ◽

G Dunn ◽

V Hough ◽

...

Keyword(s):

Head And Neck ◽

Tumour Response ◽

Interleukin 10 ◽

Th2 Cells ◽

Enzyme Linked Immunosorbent Assay ◽

Tumour Stage ◽

T Helper ◽

Serum Cytokine ◽

Cytokine Levels ◽

Helper Type

Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy. It is the most common neoplasm arising in the upper aerodigestive tract.Interleukin (IL) 12 and IL-18 are cytokines which have a major anti-tumour activity via stimulation of a T-helper type 1 (Th1) immune response. Interleukin 10, a potent antagonist of IL-12, is a cytokine which possesses immunosuppressive activity mainly produced via T-helper type 2 (Th2) cells. Studies of other types of cancer have shown that the level of IL-12 in serum or tissues is suppressed and/or the IL-10 level is increased, suggesting that there is an impaired cell-mediated anti-tumour response.The aim of this study was to measure pre-operative serum cytokine concentrations in HNSCC patients in order to detect any changes in IL-10, IL-12 and IL-18, compared with non-tumour controls. The relationship between cytokine levels and standard clinicopathological features, including tumour site, tumour stage and presence of nodal metastasis, was also examined.Fifty-seven patients with primary HNSCC were prospectively recruited, together with 40 non-tumour control patients with a similar age and sex distribution. Serum cytokine levels were measured using commercial quantitative enzyme-linked immunosorbent assay.The HNSCC patients had significantly lower IL-12 levels (median; interquartile range) than controls (42.8 pg/ml, 26.2–61.6 vs 52.3 pg/ml, 37.5–113.7; p=0.018). Also, patients were more likely to have detectable IL-10 levels than were controls, as IL-10 was positive in 27/55 patients but in only 9/39 controls (p=0.011). Furthermore, IL-10 detectability varied according to primary site, being more commonly observed in hypopharyngeal and laryngeal tumours, and IL-10 was more likely to be detected with advanced tumour stage (T3 and T4). No differences in IL-18 levels were observed between patients and controls (p=0.169).These results suggest (in agreement with studies on other solid malignancies) that HNSCC causes a significant change in the serum levels of specific Th1 and Th2 cytokines, producing an in vivo environment that is unlikely to promote an effective cell-mediated anti-tumour response.

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