Search

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. AD affects 10–20% of children worldwide and persists into adulthood in a minority of cases, affecting approximately 2–3% of the adult population, with an increased prevalence over the past decades in developed countries. Atopy is a genetic tendency to overproduce IgE class antibodies in response to common antigens found in the environment. Concurrence of different atopy such as allergic rhinitis or asthma in children with AD is estimated at 80%. AD is characterized by a vicious cycle of an allergic immune response. The emerging picture of the AD is a complex disorder with barrier dysfunction, immunological, genetic and environmental factors all playing key roles. Patients with severe or persistent disease and their families experience significant impairment in their quality of life, and in addition, AD places a heavy economic burden on society as a whole. Pathogenesis, the role of the epidermal barrier, mechanisms of cells apoptosis, the role of T cells and cytokines in AD are discussed in this article.

Human Th17 pro-inflammatory cells are currently defined as cells that produce IL-17A and F, tumor necrosis factor (TNF)-α, IL-6, IL-21, IL-22 and IL-23. Recently discovered related molecules are forming a family of cytokines, the IL-17 family, IL-17A, IL-17B, IL-17C, IL-17D, IL-17E and IL-17F. The associated receptors for the IL-17 family identified are IL-17R, IL-17RH1, IL-17RL (receptor like), IL-17RD and IL-17RE. This review introduces the roles of IL-17 and Th17 cells in human autoimmune diseases. Studies have shown that T cells with inflammatory effects on epithelial, endothelial and fibroblast cells express IL-17. Th17 cells are supposed to be involved in various autoimmune diseases, such as rheumatoid arthritis, psoriasis, multiple sclerosis, and inflammatory bowel diseases. Base on the biologic functions and regulation, IL-17 has regulatory roles in host defense and chronic inflammation which result in tissue damage and autoimmunity. So the IL-17 links links innate and adaptive immunity and has both beneficial and pathological effects on the immune system. This paper will focus on the possible roles of IL-17 in autoimmune diseases, a fundamental player in immune regulation.

Background & aimsIn our previous study, a Seesaw model was proposed for the fluctuation of crucial anti- (IL-10) and pro-inflammatory (Il-6 & IL-17A) cytokines through vitamin D3. In this paper, however, it is intended to extend the mentioned model by assessing the expression mRNA levels of IL-27 and TGF-β1 as well as the changes of plasma levels of IL-27, TGF-β1, IL-17A, IL-10, and IL-6 after treatment by vitamin D3.MethodVenous blood samples were drawn from Healthy Participants (HP, n = 25) and First-Degree Relative Participants (FDRP, n = 25) as control groups and Multiple Sclerosis Participants (MSP, n = 25) before and after eight weeks of supplementation with 50000 IU vitamin D3. The mRNA expression and plasma concentrations were gauged by using Real-Time PCR and ELISA assay, respectively.ResultsThe mRNA surfaces of IL-27, as well as TGF-β1, were up-regulated. However, the plasma levels of TGF-β1, IL-17A, and IL-6 were significantly different among the three groups. In addition, the plasma levels of IL-27, TGF-β1, IL-10, IL-17A, and IL-6 significantly changed following the administration of vitamin D3.ConclusionThe findings of this paper illustrate that anti-inflammatory cytokines could have a key role in immunomodulatory functions due to their anti-inflammatory functions. To conclude, this might contribute to preventing the pathophysiological process of MS. Also, the proposed model could be used as a preventive way on disposed people to multiple sclerosis, particularly in first degree relatives of these patients.

There is a constant cross-talk between our immune system and the colonizing microbiota. The gut resident bacteria produce a broad range of molecules with regulatory activities in both local and distal tissues. Staphylococcus (S.) aureus is a commensal bacterium with high pathogenic potential due to production of several potent virulence factors including staphylococcal enterotoxins (SEs). These SEs are known to induce overwhelming T cell responses, which can result in a serious condition known as toxic shock syndrome. In contrast, several species of bacteria from the genus Lactobacillus exhibit probiotic features and promote beneficial physiological and immunological effects in its host. The underlying mechanisms behind bacterial activation and regulation of peripheral lymphocytes remain elusive. In this thesis, we explored how secreted factors present in the cell free supernatants (CFS) of cultured S. aureus and lactobacilli mechanistically impact the activation of different types of T cells and NK cells. In paper I, we investigated the influence of S. aureus-CFS and SEA on regulatory T cells and found that despite de novo induction of FOXP3 expression, TREG cells also produced pro-inflammatory cytokines, which associated with CD161-expression. In paper II, we could show that S. aureus-CFS and SEA induce proliferation, cytotoxicity and cytokine production in conventional and unconventional T- and NK cells. Moreover, we also showed that the lactobacilli-CFS were able to dampen immune cell activation, which was partly linked to lactobacilli-derived lactate. In paper III, we continued to investigate the mechanism behind Lactobacillus-mediated dampening of induced lymphocyte responses and identified extracellular membrane vesicles to be one of the main components involved in Lactobacillus-mediated regulation of cytokine responses. Other observations made in paper II brought about several questions regarding the ability of SEs to activate unconventional T- and NK cells, which lacks certain receptors known to be required for SE-mediated activation of conventional T cells. In paper IV, we therefore investigated the mechanism behind SE-mediated activation of γδ T-, MAIT- and NK cells and found that SEs indirectly activated γδ T- and NK cells, which required the presence of conventional αβ T cells. In summary, this thesis presents novel insights into how soluble components from bacteria modulate immune cell responses and extends the general understanding of bacterial influence on peripheral immunity. At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Submitted. Paper 4: Manuscript.

trans-Sialidase from Trypanosoma cruzi (Tc-TS) belongs to a superfamily of proteins that may have enzymatic activity. While enzymatically active members (Tc-aTS) are able to transfer sialic acid (SIA) from the host cell sialyl-glycoconjugates onto the parasite or to other molecules on the host cell surface, the inactive members (Tc-iTS) are characterized by their lectinic properties. Over the last ten years, several papers demonstrated that, individually, Tc-aTS or Tc-iTS is able to modulate several biological events. Since the genes encoding Tc-iTS are present in the same copy number as those encoding Tc-aTS, and both proteins portray similar substrate-specificities as well, it would be plausible to speculate that such molecules may compete for the same sialyl-glycan structures and govern numerous immunobiological phenomena. However, their combined effect has never been evaluated in the course of an acute infection. In this study, we investigated the ability of both proteins to modulate the production of inflammatory signals, as well as the homing of T cells to the cardiac tissue of infected mice, events that usually occur during the acute phase of T. cruzi infection. The results showed that the intravenous administration of Tc-iTS, but not Tc-aTS protected the cardiac tissue from injury caused by reduced traffic of inflammatory cells. In addition, the ability of Tc-aTS to modulate the production of inflammatory cytokines was attenuated and/or compromised when Tc-iTS was co-injected in the same proportions. These results suggest that although both proteins present structural similarities and compete for the same sialyl-glycan epitopes, they might present distinct immunomodulatory properties on T cells following T. cruzi infection.