WHAT IS IMMUNE TOLERANCE? (and how to nutritionally stimulate Tregs)
What is immune tolerance?
Immune tolerance describes how the immune system adapts to tolerate certain proteins that are not harmful.
You want to have immune tolerance to food, beneficial gut microbes, pregnancy, and your own cells—without it you can experience food allergies, inflammation, and autoimmunity.
What are Tregs?
This tolerance is primarily regulated by white blood cells called Tregs.
Tregs suppress and "calm down" the inflammatory response of other immune cells.
Tregs can be stimulated to improve conditions that involve an overreaction of the immune system, like autoimmunity, asthma, psoriasis, allergies and hypersensitivities, gut issues, and cardiovascular and metabolic diseases.
The two main T cell responses are Th1 and Th2 reactions. They occur in balance with one another, like a teeter-totter. Tregs promote tolerance of food and balance between both responses, reducing hypersensitivities, allergies, and autoimmunity.
Nutrients to Stimulate Tregs
NAC
ALA
berberine
lycopene
taurine
olive leaf
green tea
papaya
turmeric
andrographis
CoQ10
glutamine
L-citrulline
cholesterol
glucose
probiotics
Health is about balance, especially when it comes to the immune system.
It is not recommended to stimulate Tregs in cases of serious infection or cancer, as those conditions necessitate a strong immune reaction (not suppression).
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References
Abdullah, M., Chai, P. S., Loh, C. Y., Chong, M. Y., Quay, H. W., Vidyadaran, S., Seman, Z., Kandiah, M., & Seow, H. F. (2011). Carica papaya increases regulatory T cells and reduces IFN-γ+ CD4+ T cells in healthy human subjects. Molecular nutrition & food research, 55(5), 803–806. https://doi.org/10.1002/mnfr.201100087
Cohen, Joe. All About Regulatory T cells (Tregs) & How to Increase Them. Self-Hacked. Retrieved from: https://selfhack.com/blog/treg/
Chen, J. H., Huang, P. H., Lee, C. C., Chen, P. Y., & Chen, H. C. (2013). A bovine whey protein extract can induce the generation of regulatory T cells and shows potential to alleviate asthma symptoms in a murine asthma model. The British journal of nutrition, 109(10), 1813–1820. https://doi.org/10.1017/S0007114512003947
Corthay A. (2009). How do regulatory T cells work?. Scandinavian journal of immunology, 70(4), 326–336. https://doi.org/10.1111/j.1365-3083.2009.02308.x
Cui, H., Cai, Y., Wang, L., Jia, B., Li, J., Zhao, S., Chu, X., Lin, J., Zhang, X., Bian, Y., & Zhuang, P. (2018). Berberine Regulates Treg/Th17 Balance to Treat Ulcerative Colitis Through Modulating the Gut Microbiota in the Colon. Frontiers in pharmacology, 9, 571. https://doi.org/10.3389/fphar.2018.00571
Dennis-Wall, J. C., Culpepper, T., Nieves, C., Jr, Rowe, C. C., Burns, A. M., Rusch, C. T., Federico, A., Ukhanova, M., Waugh, S., Mai, V., Christman, M. C., & Langkamp-Henken, B. (2017). Probiotics (Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2) improve rhinoconjunctivitis-specific quality of life in individuals with seasonal allergies: a double-blind, placebo-controlled, randomized trial. The American journal of clinical nutrition, 105(3), 758–767. https://doi.org/10.3945/ajcn.116.140012
Dimeloe, S., Nanzer, A., Ryanna, K., & Hawrylowicz, C. (2010). Regulatory T cells, inflammation and the allergic response-The role of glucocorticoids and Vitamin D. The Journal of steroid biochemistry and molecular biology, 120(2-3), 86–95. https://doi.org/10.1016/j.jsbmb.2010.02.029
Dong C. (2021). Cytokine Regulation and Function in T Cells. Annual review of immunology, 39, 51–76. https://doi.org/10.1146/annurev-immunol-061020-053702
Eggenhuizen PJ, Ng BH, Ooi JD. Treg Enhancing Therapies to Treat Autoimmune Diseases. Int J Mol Sci. 2020 Sep 23;21(19):7015. doi: 10.3390/ijms21197015. PMID: 32977677; PMCID: PMC7582931.
Ehteshamfar, S. M., Akhbari, M., Afshari, J. T., Seyedi, M., Nikfar, B., Shapouri-Moghaddam, A., Ghanbarzadeh, E., & Momtazi-Borojeni, A. A. (2020). Anti-inflammatory and immune-modulatory impacts of berberine on activation of autoreactive T cells in autoimmune inflammation. Journal of cellular and molecular medicine, 24(23), 13573–13588. https://doi.org/10.1111/jcmm.16049
Fisher SA, Rahimzadeh M, Brierley C, Gration B, Doree C, Kimber CE, Plaza Cajide A, Lamikanra AA, Roberts DJ. The role of vitamin D in increasing circulating T regulatory cell numbers and modulating T regulatory cell phenotypes in patients with inflammatory disease or in healthy volunteers: A systematic review. PLoS One. 2019 Sep 24;14(9):e0222313. doi: 10.1371/journal.pone.0222313. PMID: 31550254; PMCID: PMC6759203.
Issazadeh-Navikas, S., Teimer, R., & Bockermann, R. (2012). Influence of dietary components on regulatory T cells. Molecular medicine (Cambridge, Mass.), 18(1), 95–110. https://doi.org/10.2119/molmed.2011.00311
Jiang, Z., & Wu, C. (2022). Reciprocal Interactions Between Regulatory T Cells and Intestinal Epithelial Cells. Frontiers in immunology, 13, 951339. https://doi.org/10.3389/fimmu.2022.951339
Kasahara, H., Kondo, T., Nakatsukasa, H., Chikuma, S., Ito, M., Ando, M., Kurebayashi, Y., Sekiya, T., Yamada, T., Okamoto, S., & Yoshimura, A. (2017). Generation of allo-antigen-specific induced Treg stabilized by vitamin C treatment and its application for prevention of acute graft versus host disease model. International immunology, 29(10), 457–469. https://doi.org/10.1093/intimm/dxx060
Kunisawa J, Hashimoto E, Ishikawa I, Kiyono H (2012) A Pivotal Role of Vitamin B9 in the Maintenance of Regulatory T Cells In Vitro and In Vivo. PLoS ONE 7(2): e32094. https://doi.org/10.1371/journal.pone.0032094
Lai, Z.-W., Hanczko, R., Bonilla, E., Caza, T.N., Clair, B., Bartos, A., Miklossy, G., Jimah, J., Doherty, E., Tily, H., Francis, L., Garcia, R., Dawood, M., Yu, J., Ramos, I., Coman, I., Faraone, S.V., Phillips, P.E. and Perl, A. (2012), N-acetylcysteine reduces disease activity by blocking mammalian target of rapamycin in T cells from systemic lupus erythematosus patients: A randomized, double-blind, placebo-controlled trial. Arthritis & Rheumatism, 64: 2937-2946. https://doi.org/10.1002/art.34502
Lee, S. H., Park, M. J., Lee, S. H., & Cho, M. L. (2016). Coenzyme Q10 Exerts Anti-Inflammatory Activity and Induces Treg in Graft Versus Host Disease. Journal of medicinal food, 19(3), 238–244. https://doi.org/10.1089/jmf.2015.3535
Lowder, T., Dugger, K., Deshane, J., Estell, K., & Schwiebert, L. M. (2010). Repeated bouts of aerobic exercise enhance regulatory T cell responses in a murine asthma model. Brain, behavior, and immunity, 24(1), 153–159. https://doi.org/10.1016/j.bbi.2009.09.011Ma, C., Ma, Z., Fu, Q., & Ma, S. (2013). Curcumin attenuates allergic airway inflammation by regulation of CD4+CD25+ regulatory T cells (Tregs)/Th17 balance in ovalbumin-sensitized mice. Fitoterapia, 87, 57–64. https://doi.org/10.1016/j.fitote.2013.02.014
Mageswary, M. U., Ang, X. Y., Lee, B. K., Chung, Y. F., Azhar, S. N. A., Hamid, I. J. A., Bakar, H. A., Roslan, N. S., Liu, X., Kang, X., Dai, L., Sreenivasan, S., Taib, F., Zhang, H., & Liong, M. T. (2022). Probiotic Bifidobacterium lactis Probio-M8 treated and prevented acute RTI, reduced antibiotic use and hospital stay in hospitalized young children: a randomized, double-blind, placebo-controlled study. European journal of nutrition, 61(3), 1679–1691. https://doi.org/10.1007/s00394-021-02689-8
Park, M. J., Moon, S. J., Lee, S. H., Yang, E. J., Min, J. K., Cho, S. G., Yang, C. W., Park, S. H., Kim, H. Y., & Cho, M. L. (2013). Curcumin attenuates acute graft-versus-host disease severity via in vivo regulations on Th1, Th17 and regulatory T cells. PloS one, 8(6), e67171. https://doi.org/10.1371/journal.pone.0067171
Regulatory T Cells. Cleveland Clinic. Retrieved from: https://my.clevelandclinic.org/health/body/23580-regulatory-t-cells
Schmitt, A. K., Puppa, M. A., Wessels, I., & Rink, L. (2022). Vitamin D3 and zinc synergistically induce regulatory T cells and suppress interferon-γ production in mixed lymphocyte culture. The Journal of nutritional biochemistry, 102, 108942. https://doi.org/10.1016/j.jnutbio.2022.108942
Spaiser, S. J., Culpepper, T., Nieves, C., Jr, Ukhanova, M., Mai, V., Percival, S. S., Christman, M. C., & Langkamp-Henken, B. (2015). Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2 Ingestion Induces a Less Inflammatory Cytokine Profile and a Potentially Beneficial Shift in Gut Microbiota in Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study. Journal of the American College of Nutrition, 34(6), 459–469. https://doi.org/10.1080/07315724.2014.983249
Tan, J., Taitz, J., Sun, S. M., Langford, L., Ni, D., & Macia, L. (2022). Your Regulatory T Cells Are What You Eat: How Diet and Gut Microbiota Affect Regulatory T Cell Development. Frontiers in nutrition, 9, 878382. https://doi.org/10.3389/fnut.2022.878382
Qiu, D., Zhang, W., Song, Z., Xue, M., Zhang, Y., Yang, Y., Tong, C., & Cai, D. (2022). Berberine suppresses cecal ligation and puncture induced intestinal injury by enhancing Treg cell function. International immunopharmacology, 106, 108564. https://doi.org/10.1016/j.intimp.2022.108564
Ushiroda, C., Takagi, T., Fuke, N., Mizushima, K., Hirai, Y., Higashimura, Y., Harusato, A., Kamada, K., Uchiyama, K., Ishikawa, T., Aizawa, K., Suganuma, H., Itoh, Y., & Naito, Y. (2022). Lycopene intake induces colonic regulatory T cells in mice and suppresses food allergy symptoms. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, 33(1), e13691. https://doi.org/10.1111/pai.13691
Wan, Y. Y., & Flavell, R. A. (2007). 'Yin-Yang' functions of transforming growth factor-beta and T regulatory cells in immune regulation. Immunological reviews, 220, 199–213. https://doi.org/10.1111/j.1600-065X.2007.00565.x
Wang, K. C., Tsai, C. P., Lee, C. L., Chen, S. Y., Lin, G. J., Yen, M. H., Sytwu, H. K., & Chen, S. J. (2013). α-Lipoic acid enhances endogenous peroxisome-proliferator-activated receptor-γ to ameliorate experimental autoimmune encephalomyelitis in mice. Clinical science (London, England : 1979), 125(7), 329–340. https://doi.org/10.1042/CS20120560
Wong, C. P., Nguyen, L. P., Noh, S. K., Bray, T. M., Bruno, R. S., & Ho, E. (2011). Induction of regulatory T cells by green tea polyphenol EGCG. Immunology letters, 139(1-2), 7–13. https://doi.org/10.1016/j.imlet.2011.04.009
Yao, Y., Chen, C. L., Yu, D., & Liu, Z. (2021). Roles of follicular helper and regulatory T cells in allergic diseases and allergen immunotherapy. Allergy, 76(2), 456–470. https://doi.org/10.1111/all.14639
Yousefi, Z., Mirsanei, Z., Bitaraf, F. S., Mahdavi, S., Mirzaii, M., & Jafari, R. (2022). Dose-dependent effects of oleuropein administration on regulatory T-cells in patients with rheumatoid arthritis: An in vitro approach. International journal of immunopathology and pharmacology, 36, 3946320221086084. https://doi.org/10.1177/03946320221086084
Zhao, G. J., Lu, Z. Q., Tang, L. M., Wu, Z. S., Wang, D. W., Zheng, J. Y., & Qiu, Q. M. (2012). Curcumin inhibits suppressive capacity of naturally occurring CD4+CD25+ regulatory T cells in mice in vitro. International immunopharmacology, 14(1), 99–106. https://doi.org/10.1016/j.intimp.2012.06.016
Zhou, Jing & Lu, Yi & Wu, Wei & Feng, Yunhai. (2021). Taurine promotes the production of CD4+CD25+FOXP3+ Treg cells through regulating IL-35/STAT1 pathway in a mouse allergic rhinitis model. Allergy, Asthma & Clinical Immunology. 17. 10.1186/s13223-021-00562-1