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The importance of psychological and physical stressors on diabetes-related immunity in a young population – an interdisciplinary approach
Högskolan i Jönköping, Hälsohögskolan, HHJ, Avd. för naturvetenskap och biomedicin. Högskolan i Jönköping, Hälsohögskolan, HHJ. Biomedicinsk plattform.
2016 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Jönköping: Jönköping University, School of Health and Welfare , 2016. , s. 117
Serie
Dissertation Series. School of Health and Welfare, ISSN 1654-3602 ; 072
Nyckelord [en]
psychological stressors, physical stressors, cellular immune system, type 1 diabetes, young population
Nationell ämneskategori
Immunologi
Identifikatorer
URN: urn:nbn:se:hj:diva-31754ISBN: 978-91-85835-71-3 (tryckt)OAI: oai:DiVA.org:hj-31754DiVA, id: diva2:968746
Disputation
2016-10-07, Forum Humanum, School of Health and Welfare, Jönköping, 13:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2016-09-16 Skapad: 2016-09-12 Senast uppdaterad: 2016-09-12Bibliografiskt granskad
Delarbeten
1. Psychological Stress in Children May Alter the Immune Response
Öppna denna publikation i ny flik eller fönster >>Psychological Stress in Children May Alter the Immune Response
2014 (Engelska)Ingår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 192, nr 5, s. 2071-2081Artikel i tidskrift (Refereegranskat) 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.

Nationell ämneskategori
Immunologi
Identifikatorer
urn:nbn:se:hj:diva-23599 (URN)10.4049/jimmunol.1301713 (DOI)000332701400011 ()24501202 (PubMedID)2-s2.0-84896524481 (Scopus ID)
Tillgänglig från: 2014-03-11 Skapad: 2014-03-11 Senast uppdaterad: 2017-12-05Bibliografiskt granskad
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
Öppna denna publikation i ny flik eller fönster >>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
Visa övriga...
2016 (Engelska)Artikel i tidskrift (Övrigt vetenskapligt) Submitted
Nationell ämneskategori
Immunologi
Identifikatorer
urn:nbn:se:hj:diva-31751 (URN)
Externt samarbete:
Tillgänglig från: 2016-09-12 Skapad: 2016-09-12 Senast uppdaterad: 2016-09-12
3. High physical activity in young children suggests positive effects by altering autoantigen-induced immune activity
Öppna denna publikation i ny flik eller fönster >>High physical activity in young children suggests positive effects by altering autoantigen-induced immune activity
2016 (Engelska)Ingår i: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 26, nr 4, s. 441-450Artikel i tidskrift (Refereegranskat) 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.

Nyckelord
Autoimmunity; Cytokines; Immune response; Physical activity; Young children
Nationell ämneskategori
Idrottsvetenskap
Identifikatorer
urn:nbn:se:hj:diva-26374 (URN)10.1111/sms.12450 (DOI)000373356600009 ()25892449 (PubMedID)2-s2.0-84961198218 (Scopus ID)
Externt samarbete:
Tillgänglig från: 2015-04-24 Skapad: 2015-04-24 Senast uppdaterad: 2017-12-04Bibliografiskt granskad
4. Endurance training during adolescence induces a pro-inflammatory response directed towards the diabetes-related autoantigen tyrosine phosphatase-2
Öppna denna publikation i ny flik eller fönster >>Endurance training during adolescence induces a pro-inflammatory response directed towards the diabetes-related autoantigen tyrosine phosphatase-2
(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nationell ämneskategori
Immunologi
Identifikatorer
urn:nbn:se:hj:diva-31750 (URN)
Tillgänglig från: 2016-09-12 Skapad: 2016-09-12 Senast uppdaterad: 2019-08-29

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