Unsaturated fatty acids (UFA) are crucial for T-cell effector functions, as they can affect the growth, differentiation, survival, and function of T cells. Nonetheless, the mechanisms by which UFA... Show moreUnsaturated fatty acids (UFA) are crucial for T-cell effector functions, as they can affect the growth, differentiation, survival, and function of T cells. Nonetheless, the mechanisms by which UFA affects T-cell behavior are ill-defined. Therefore, we analyzed the processing of oleic acid, a prominent UFA abundantly present in blood, adipocytes, and the fat pads surrounding lymph nodes, in CD4+ T cells. We found that exogenous oleic acid increases proliferation and enhances the calcium flux response upon CD3/CD28 activation. By using a variety of techniques, we found that the incorporation of oleic acid into membrane lipids, rather than regulation of cellular metabolism or TCR expression, is essential for its effects on CD4+ T cells. These results provide novel insights into the mechanism through which exogenous oleic acid enhances CD4+ T-cell function. Show less
Background: The Nature Step to Respiratory Health was the overarching theme of the 12th General Meeting of the Global Alliance against Chronic Respiratory Diseases (GARD) in Helsinki, August 2018.... Show moreBackground: The Nature Step to Respiratory Health was the overarching theme of the 12th General Meeting of the Global Alliance against Chronic Respiratory Diseases (GARD) in Helsinki, August 2018. New approaches are needed to improve respiratory health and reduce premature mortality of chronic diseases by 30% till 2030 (UN Sustainable Development Goals, SDGs). Planetary health is defined as the health of human civilization and the state of the natural systems on which it depends. Planetary health and human health are interconnected, and both need to be considered by individuals and governments while addressing several SDGs.Results: The concept of the Nature Step has evolved from innovative research indicating, how changed lifestyle in urban surroundings reduces contact with biodiverse environments, impoverishes microbiota, affects immune regulation and increases risk of NCDs. The Nature Step calls for strengthening connections to nature. Physical activity in natural environments should be promoted, use of fresh vegetables, fruits and water increased, and consumption of sugary drinks, tobacco and alcohol restricted. Nature relatedness should be part of everyday life and especially emphasized in the care of children and the elderly. Taking "nature" to modern cities in a controlled way is possible but a challenge for urban planning, nature conservation, housing, traffic arrangements, energy production, and importantly for supplying and distributing food. Actions against the well-known respiratory risk factors, air pollution and smoking, should be taken simultaneously.Conclusions: In Finland and elsewhere in Europe, successful programmes have been implemented to reduce the burden of respiratory disorders and other NCDs. Unhealthy behaviour can be changed by well-coordinated actions involving all stakeholders. The growing public health concern caused by NCDs in urban surroundings cannot be solved by health care alone; a multidisciplinary approach is mandatory. Show less
Kidney transplantation is the preferred treatment of patients with end stage renal disease, as it provides longer patient survival and better quality of life compared to dialysis. Prediction of... Show moreKidney transplantation is the preferred treatment of patients with end stage renal disease, as it provides longer patient survival and better quality of life compared to dialysis. Prediction of DGF, response to steroid resistant rejection and long-term graft outcome remain difficult when using merely clinical parameters. Numerous studies have reported on the predictive value of molecular markers for AR and worse graft outcome. However, the heterogeneity of AR and the variation among transplant centers leads to controversial results and preclude a more general clinical application. In the first part of this thesis, we aimed to investigate the molecular markers of steroid resistance and long-term graft survival on the basis of acute rejection biopsies. In the second part, we focused on genetic variants associated with acute rejection in kidney transplantation. In the final part we described the possible immune regulatory effect of S100 calcium binding proteins. Show less
Type 1 diabetes is a T-cell mediated autoimmune disease in which the insulin producing cells in the islets of Langerhans are destroyed. No cure exists yet, but multiple types of immune suppressive... Show moreType 1 diabetes is a T-cell mediated autoimmune disease in which the insulin producing cells in the islets of Langerhans are destroyed. No cure exists yet, but multiple types of immune suppressive regimens are explored. In this thesis I studied the opportunities to dampen autoimmunity in type 1 diabetes, with the focus on the possibility of using tolerogenic dendritic cells loaded with islet antigens as cell therapy in patients with type 1 diabetes. Tolerogenic DCs appear suitable candidates to modulate T-cell response at different levels and are able to induce antigen specific regulatory T-cells, utilizing various mechanisms to suppress pro-inflammatory responses. Hence, the chance for successful control of autoimmunity in patients treated with tolerogenic DC therapy may be increased compared to monotherapy. Tolerogenic DCs as cell therapy have the potential to modulate the immune system. Although replacement or enhancement of insulin producing beta-cells is warranted, focusing on diminishing the causal pathology, the immune attack on the islets of Langerhans, could be a preferential option, as it is still difficult to challenge existing autoimmunity with the current arsenal of immunosuppressive drugs. This tissue-specific intervention cell therapy might offer new opportunities for the treatment of type 1 diabetes. Show less
Helminth parasites are able to induce immune regulation in their host. Suppression of the host immune system is beneficial for both the parasite, by inhibiting anti-parasite immunity, and for the... Show moreHelminth parasites are able to induce immune regulation in their host. Suppression of the host immune system is beneficial for both the parasite, by inhibiting anti-parasite immunity, and for the host, by preventing tissue damage due to excessive inflammation. There are indications that in countries where parasites have been eliminated the immune regulatory network is impaired, leading to inflammatory diseases such as allergies and asthma. An important player in immune regulation is the regulatory T cell (Treg). We have shown that the number and/or function of Tregs were indeed enhanced in several helminth and also malaria infections in humans. Tregs were not only involved in suppression of anti-parasite responses, but also of responses to other infections or vaccines. We further investigated the effect of helminth elimination in a randomized placebo-controlled trial. Treatment of helminths led to a strong increase in __mainly pro-inflammatory__ immune responses, which confirms the importance of immune regulation during infection. Furthermore, the prevalence of malaria was transiently increased and allergy was slightly on the rise in treated school children. These results further endorse the possible beneficial effects of helminthic therapy, which is currently being tested in a number of clinical trials. Show less
This thesis consists of two parts, focusing on CD4+CD25+ regulatory T cells (Tregs) (Part I) and IgG glycosylations (Part II), respectively. Part I (Chapter 2-5) is mainly dedicated to a better... Show moreThis thesis consists of two parts, focusing on CD4+CD25+ regulatory T cells (Tregs) (Part I) and IgG glycosylations (Part II), respectively. Part I (Chapter 2-5) is mainly dedicated to a better identification/characterization and generation of functional human Tregs in vitro. In Chapter 2, we investigated the dynamics of endogenous FOXP3 expression and its relation to the suppressive function in activated human CD4+ T cells. In Chapter 3, we discovered an inverse correlation between membrane-bound TNF-alpha expression and cell suppressive abilities within human CD4+CD25++ T-cell compartment. In Chapter 4 & 5, we developed efficient approaches to consistently convert effector T cells into Tregs both in mice and humans. The underlying mechanisms responsible for the inconsistency in Treg conversion were unraveled as well. Part II (Chapter 6-7) aims to analyze the glycosylation pattern of antigen-specific antibodies and to obtain more insights on how glycosylation is regulated during an active immune response. Chapter 6 describes a method for the microscale purification and Fc-glycosylation analysis of auto-antibodies in patients with rheumatoid arthritis. In Chapter 7, we identified, by using an in vitro culture system, some factors that can influence the gylcan pattern of secreted IgG1 during the activation and differentiation of B cells. Show less
