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The importance of psychological and physical stressors on diabetes-related immunity in a young population – an interdisciplinary approach
Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: The prevalence of immunological disorders such as type 1 diabetes (T1D) is increasingly common amongst children, adolescents and young adults. There is also an increase in psychosomatic symptoms (depression, insomnia, anxiety, headaches and fatigue etc.) as well as a decrease in physical activity amongst young people, affecting the well-being and overall health of our younger population. It is therefore important to study the effects of psychological and physical stressors on the immune system, to evaluate their impact on juvenile health.

Aim: This thesis explores the impact of psychological and physical stressors on the cellular immune system with special focus on diabetes-related immunity in a young population, using an interdisciplinary approach.

Method: When exploring the impact of psychological and physical stressors such as psychological stress due to exposure to psychological stressful experiences or degree of physical activity/training on the cellular immune system in children, adolescents and young women, peripheral blood mononuclear cells (PBMC) were stimulated with antigens (tetanus toxoid (TT) and β-lactoglobulin (βLG)) as well as diabetes-related autoantigens (insulin, heat shock protein 60 (HSP60), tyrosine phosphatase-2 (IA-2) and glutamic acid decarboxylase 65 (GAD65)) and secreted cytokines and chemokines were measured by multiplex fluorochrome technique (Luminex). Populations of Thelper (Th) cells (CD4+), T-cytotoxic (Tc) cells (CD8+), B cells (CD19+), Natural Killer (NK) cells (CD56+CD16+) as well as regulatory T (Treg) cells (CD4+CD25+FoxP3+CD127-), and their expression of CD39 and CD45RA were studied by flow cytometry. Diabetes-related parameters (glucose, C-peptide,proinsulin, pancreatic polypeptide and peptide YY) were measured to studyβ-cell activity and appetite regulation and cortisol was used as a biological marker for psychological and physical stress.

Results: Children in families exposed to psychological stress showed an imbalanced cellular immune response as well as an increased immune response towards diabetes-related autoantigens. Also, previous exposure to psychological stress as well as current exposure to psychological stress in young women showed an increased immune response towards diabetes-related autoantigens. Further, previous exposure to psychological stress in young women showed increased numbers of circulating CD56+CD16+ NK cells as wellas decreased numbers of circulating CD4+CD25+FoxP3+CD127- Treg cells. High physical activity in children showed decreased spontaneous immune response as well as a decreased immune response towards diabetes-related autoantigens, while low physical activity in children showed an increased immune response towards diabetes-related autoantigens. Further, endurance training in adolescents, especially in adolescent males and young adolescents, showed an increased immune response towards the diabetes-related autoantigen IA-2.

Conclusion: It is evident that psychological and physical stressors such as exposure to psychological stress and degree of physical activity/training impact the cellular immune system. Experiences associated with psychological stress seem to have a negative effect on the cellular immune system in a young population, causing an imbalance in the immune system that could possibly induce diabetes-related immunity. High physical activity in children seems to have a protective effect against diabetes-related immunity. In contrast, low physical activity in children and endurance training in adolescents seems to induce diabetes-related immunity. It is very likely that psychological stressful experiences, low physical activity and intense training such as endurance training all play important roles in the immunological process leading to the development of type 1 diabetes.

Place, publisher, year, edition, pages
Jönköping: Jönköping University, School of Health and Welfare , 2016. , 117 p.
Series
Hälsohögskolans avhandlingsserie, ISSN 1654-3602 ; 072
Keyword [en]
psychological stressors, physical stressors, cellular immune system, type 1 diabetes, young population
National Category
Immunology
Identifiers
URN: urn:nbn:se:hj:diva-31754ISBN: 978-91-85835-71-3OAI: oai:DiVA.org:hj-31754DiVA: diva2:968746
Public defence
2016-10-07, Forum Humanum, School of Health and Welfare, Jönköping, 13:00 (English)
Opponent
Supervisors
Available from: 2016-09-16 Created: 2016-09-12 Last updated: 2016-09-12Bibliographically approved
List of papers
1. Psychological Stress in Children May Alter the Immune Response
Open this publication in new window or tab >>Psychological Stress in Children May Alter the Immune Response
2014 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 192, no 5, 2071-2081 p.Article in journal (Refereed) Published
Abstract [en]

Psychological stress is a public health issue even in children and has been associated with a number of immunological diseases. The aim of this study was to examine the relationship between psychological stress and immune response in healthy children, with special focus on autoimmunity. In this study, psychological stress was based on a composite measure of stress in the family across the domains: 1) serious life events, 2) parenting stress, 3) lack of social support, and 4) parental worries. PBMCs, collected from 5-y-old high-stressed children (n = 26) and from 5-y-old children without high stress within the family (n = 52), from the All Babies In Southeast Sweden cohort, were stimulated with Ags (tetanus toxoid and β-lactoglobulin) and diabetes-related autoantigens (glutamic acid decarboxylase 65, insulin, heat shock protein 60, and tyrosine phosphatase). Immune markers (cytokines and chemokines), clinical parameters (C-peptide, proinsulin, glucose), and cortisol, as an indicator of stress, were analyzed. Children from families with high psychological stress showed a low spontaneous immune activity (IL-5, IL-10, IL-13, IL-17, CCL2, CCL3, and CXCL10; p < 0.01) but an increased immune response to tetanus toxoid, β-lactoglobulin, and the autoantigens glutamic acid decarboxylase 65, heat shock protein 60, and tyrosine phosphatase (IL-5, IL-6, IL-10, IL-13, IL-17, IFN-γ, TNF-α, CCL2, CCL3, and CXCL10; p < 0.05). Children within the high-stress group showed high level of cortisol, but low level of C-peptide, compared with the control group (p < 0.05). This supports the hypothesis that psychological stress may contribute to an imbalance in the immune response but also to a pathological effect on the insulin-producing β cells.

National Category
Immunology
Identifiers
urn:nbn:se:hj:diva-23599 (URN)10.4049/jimmunol.1301713 (DOI)
Available from: 2014-03-11 Created: 2014-03-11 Last updated: 2016-09-12Bibliographically approved
2. Psychological stress affects the numbers of circulating CD56+CD16+ and CD4+CD25+FoxP3+CD127- cells and induce an immune response towards type 1 diabetes-related autoantigens in young women
Open this publication in new window or tab >>Psychological stress affects the numbers of circulating CD56+CD16+ and CD4+CD25+FoxP3+CD127- cells and induce an immune response towards type 1 diabetes-related autoantigens in young women
Show others...
2016 (English)Article in journal (Other academic) Submitted
National Category
Immunology
Identifiers
urn:nbn:se:hj:diva-31751 (URN)
External cooperation:
Available from: 2016-09-12 Created: 2016-09-12 Last updated: 2016-09-12
3. High physical activity in young children suggests positive effects by altering autoantigen-induced immune activity
Open this publication in new window or tab >>High physical activity in young children suggests positive effects by altering autoantigen-induced immune activity
2016 (English)In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 26, no 4, 441-450 p.Article in journal (Refereed) Published
Abstract [en]

Physical activity in children is associated with several positive health outcomes such as decreased cardiovascular risk factors, improved lung function, enhanced motor skill development, healthier body composition, and also improved defense against inflammatory diseases. We examined how high physical activity vs a sedentary lifestyle in young children influences the immune response with focus on autoimmunity. Peripheral blood mononuclear cells, collected from 55 5-year-old children with either high physical activity (n = 14), average physical activity (n = 27), or low physical activity (n  = 14), from the All Babies In Southeast Sweden (ABIS) cohort, were stimulated with antigens (tetanus toxoid and beta-lactoglobulin) and autoantigens (GAD65, insulin, HSP60, and IA-2). Immune markers (cytokines and chemokines), C-peptide and proinsulin were analyzed. Children with high physical activity showed decreased immune activity toward the autoantigens GAD65 (IL-5, P < 0.05), HSP60 and IA-2 (IL-10, P < 0.05) and also low spontaneous pro-inflammatory immune activity (IL-6, IL-13, IFN-γ, TNF-α, and CCL2 (P  < 0.05)) compared with children with an average or low physical activity. High physical activity in young children seems to have positive effects on the immune system by altering autoantigen-induced immune activity.

Keyword
Autoimmunity; Cytokines; Immune response; Physical activity; Young children
National Category
Sport and Fitness Sciences
Identifiers
urn:nbn:se:hj:diva-26374 (URN)10.1111/sms.12450 (DOI)000373356600009 ()25892449 (PubMedID)2-s2.0-84961198218 (ScopusID)
External cooperation:
Available from: 2015-04-24 Created: 2015-04-24 Last updated: 2016-09-12Bibliographically approved
4. Endurance training during adolescence induces a pro-inflammatory response directed towards the diabetes-related autoantigen tyrosine phosphatase-2
Open this publication in new window or tab >>Endurance training during adolescence induces a pro-inflammatory response directed towards the diabetes-related autoantigen tyrosine phosphatase-2
(English)Manuscript (preprint) (Other academic)
National Category
Immunology
Identifiers
urn:nbn:se:hj:diva-31750 (URN)
External cooperation:
Available from: 2016-09-12 Created: 2016-09-12 Last updated: 2016-09-12

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