T-Regs: Guardians of the Innerverse

In the intricate realm of our immune system, regulatory T-cells (Tregs) shine as guardians of our inner physiological well-being, maintaining balance to prevent our body's defences from turning against itself or allowing invading diseases to exploit our immune system. Recent research illuminates their crucial role in sustaining good health, especially concerning cancer, autoimmune diseases, and aging. It's noteworthy that much of the science and underlying understanding is new, emanating from research findings from the past two years. 
Vitruvian Man Image Source: DreamsTime
Tregs: The Immune System's Guardians

Picture this: your immune system is like an army, ever ready to defend against invaders. But just like any army, it needs commanders to maintain order. Enter Tregs, the peacekeepers of our immune system. Their job? To prevent overzealous immune responses that could harm our own tissues. Without them, the immune system can go into overdrive, leading to autoimmune diseases like rheumatoid arthritis, multiple sclerosis, and Lupus, or leaving our immune defenses vulnerable to cancers and viruses such as HIV-AIDS and COVID.

Tregs and Autoimmune Diseases: Finding Balance

In autoimmune diseases, the finely tuned balance maintained by Tregs is disrupted, causing the immune system to attack the body's own tissues. This breakdown in Treg regulation leads to conditions such as rheumatoid arthritis (affecting the joints), Hashimoto’s thyroiditis (targeting the thyroid), multiple sclerosis (impacting the central nervous system), and lupus (causing systemic issues).

Obesity can also be viewed through this lens, as a dysregulation of adipose tissue Tregs leads to similar immune dysfunction (to follow). In these cases, the crucial protective role of Tregs is diminished, leaving vital body regions vulnerable to attacks from our own immune defences.

Tregs in Cancer: A Double-Edged Sword

When it comes to cancer, however, Tregs play a complex dual role. On one hand, they can co-opt Treg cells in their own defence, suppressing anti-tumour immune responses and aiding cancer cells in evading detection. Yet, on the other hand, endurance exercise has been shown to recruit Tregs to muscles, countering their cancer-supportive effects. It's like a tug-of-war within our bodies, where the outcome depends on various factors such as fitness level and the type and stage of cancer.

HIV, COVID, and Tregs: Complex Interactions

Both Human Immunodeficiency Virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, employ intricate strategies to manipulate regulatory T cells (Tregs) to their advantage. HIV targets Tregs to suppress immune responses, facilitating viral persistence and disease progression. Similarly, SARS-CoV-2 exploits Tregs to dampen immune reactions, allowing viral replication and severe illness in COVID-19 patients. 

Additionally, emerging evidence suggests that dysregulation of Tregs contributes to Long-COVID and the increased incidence of autoimmune diseases affecting roughly 10% of those who had COVID-19. This includes both symptomatic and asymptomatic cases, although disease severity is associated with a higher risk of autoimmune complications. There is also an increased risk of heart-related issues for healthy, fit men under 40 when exercising strenuously during or after even having asymptomatic COVID-19.

A conclusion is that having fewer Tregs  enhances the likelihood of long COVID development in addition to contributing to the disease's poor prognosis. Dysregulation of Tregs by both viruses generally leads to compromised immune function and worse clinical outcomes.

Tregs in Fat Tissue and Obesity

Regulatory T cells (Tregs) in fat tissue help control inflammation and metabolism. In obesity, the number of these Tregs decreases, leading to more inflammation and insulin resistance. Research shows that in obese people, these Tregs become dysfunctional due to increased inflammation Research shows that inobese people, these Tregs become dysfunctional due to increased inflammation.

Fat tissue Tregs in obese individuals have higher levels of proteins that indicate exhaustion and are less effective at controlling other cells compared to Tregs in the blood. Studies reveal that exhausted fat tissue Tregs have different activity patterns, contributing to more inflammation and metabolic problems in obesity.

Tregs and Ageing: Declining Immune Vigilance

As we age, Tregs gradually lose their ability to maintain immune balance, rendering individuals more susceptible to autoimmune diseases, cancer, and other lifestyle-related conditions such as depression, lethargy, memory loss, dementia, osteoporosis, arthritis, Parkinson's disease, sarcopenia, diabetes, and coronary artery disease. Sedentary lifestyles and chronic stress exacerbate Treg dysfunction, while regular exercise and healthy habits can help mitigate it. Early intervention is crucial for preserving immune health and preventing age-related diseases, underscoring the importance of nurturing Tregs for lifelong well-being.

The CBD Connection

Research suggests that cannabinoids, both natural (endocannabinoids derived from normal nutrition) and synthetic (exocannabinoids from ingested CBD), may aid in disease treatment by promoting regulatory T cells (Tregs) that maintain immune balance aid in disease treatment by promoting healthy functional regulatory T cells (Tregs) that maintain immunebalance. Exercise in particular has been shown to stimulate the endocannabinoid system (or ECS), boosting natural endocannabinoid production. By triggering cannabinoid receptors, both natural (through normal production or exercise) and synthetic cannabinoids can increase functional Tregs, promoting immune balance and potential therapeutic benefits.

Exercise: A Friend or Foe of Tregs?

Not all exercise is created equal when it comes to stimulating the endocannabinoid system (ECS) and boosting regulatory T cells (Tregs). Given the pivotal role of Tregs in combating inflammation, engaging in physical activities that stimulate the immune system without sufficient Treg support may lead to adverse health outcomes. Intense workouts, particularly for those lacking conditioning, can induce muscle damage and inflammation, potentially interfering with Treg function. Incorrect physical activity can trigger an inflammatory cytokine storm similar to that experienced with severe COVID-19. A study from November 2023 on unconditioned mice revealed that treadmill activity triggered unchecked muscle inflammation, characterized by the rapid accumulation of inflammation-promoting cells and swollen mitochondria in their hind leg muscles. This underscores the necessity of adopting suitable exercise routines. Combined strength and endurance exercises, when executed correctly, have demonstrated the ability to augment Treg function, thus promoting overall health and well-being.

The Importance of Choosing the Right Exercise

Understanding the nuances of Treg function underscores the importance of choosing the right exercise regimen. While intense workouts may have their place for some, they can pose risks, especially for those with existing health conditions. Instead, focusing on activities that promote Treg function, such as moderate endurance exercise and supportive strength training, can offer benefits without the drawbacks.

Conclusion: Nurturing Tregs for Better Health

In the intricate dance of our immune system, Tregs emerge as key players, orchestrating a delicate balance between protection and regulation. Understanding their role in disease formation as well as exercise highlights the importance of nurturing Treg function for better health outcomes. By choosing the right exercise regimen and supporting Treg function, we can empower our immune system to safeguard our well-being for years to come.

Final Note on Inflammation

Understanding the delicate balance of our immune system involves navigating through complex interactions, one of which is the IL-6 Enigma discussed in a previous post. This protein molecule, when produced by the immune system, can have a dysregulatory effect, contributing to inflammation. However, during activities like exercise, IL-6 activated by active muscles takes on an anti-inflammatory role, enhancing their cellular protective effect. Specifically, IL-6 produced by the muscles serves as a crucial catalyst for healthy Tregs function and production, while IL-6 produced by the immune system contributes to its dysregulation. However, because exercise can also trigger the immune system, a delicate balance needs to be observed. This duality underscores the importance of not only comprehending the components of our immune system but also recognizing the environmental factors that influence their function. 

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