Psychological stress to ovalbumin peptide-specific T-cell receptor transgenic mice impairs the suppressive ability of type 1 regulatory T cell.

Numerous diseases of the immune system can be traced back to the malfunctioning of the regulatory T cells. The aetiology is unclear. Psychological stress can cause disruption to the immune regulation. The synergistic effects of psychological stress and immune response on immune regulation have yet to be fully understood. The intention of this study is to analyse the interaction between psychological stress and immune responses and how it affects the functional status of type 1 regulatory T (Tr1) cells. In this study, ovalbumin peptide T-cell receptor transgenic mice were utilised. Mice were subjected to restraint stress to induce psychological stress. An airway allergy murine model was established, in which a mouse strain with RING finger protein 20 (Rnf20)-deficient CD4+ T cells were used. The results showed that concomitant exposure to restraint stress and immune response could exacerbate endoplasmic reticulum stress in Tr1 cells. Corticosterone was responsible for the elevated expression of X-box protein-1 (XBP1) in mouse Tr1 cells after exposure to both restraint stress and immune response. XBP1 mediated the effects of corticosterone on inducing Rnf20 in Tr1 cells. The reduction of the interleukin-10 expression in Tr1 cells was facilitated by Rnf20. Inhibition of Rnf20 alleviated experimental airway allergy by restoring the immune regulatory ability of Tr1 cells. In conclusion, the functions of Tr1 cells are negatively impacted by simultaneous exposure to psychological stress and immune response. Tr1 cells' immune suppressive functions can be restored by inhibiting Rnf20, which has the translational potential for the treatment of diseases of the immune system.

Endoplasmic reticulum stress interferes with the development of type 1 regulating T cells.

BACKGROUND: A variety of stimuli can cause endoplasmic reticulum (ER) stress, which is a common cellular reaction. It is not yet clear how ER stress contributes to the pathogenesis of ulcerative colitis (UC). The deregulation of regulatory T cell (Treg) is associated with UC. The goal of this study is to shed light on how ER stress affects Treg's development. METHODS: CD4+ CD25- T cells were isolated from blood samples collected from UC patients and healthy control (HC) subjects. ER stress-associated molecule expression in CD4+ CD25- T cell was assessed by RNA sequencing and RT-qPCR. RESULTS: The presence of ER stress in peripheral CD4+ CD25- T cells was observed in patients with UC compared to HC subjects. The induction of ER stress in HC CD4+ CD25- T cells by polyclonal activation was made worse by the presence of 3-methyl-4-nitrophenol (MNP; a common environmental pollutant). Exposure to MNP in culture resulted in an increase in the expression of ring finger protein 20 (Rnf20) in CD4+ CD25- T cells. The synergistic effects of MNP and ER stress on the reduction of IL-10 levels in CD4+ CD25- T cells are mediated by Rnf20, which prevents the development of Tr1 cells. Inhibition of Rnf20 resulted in the development of Tr1 cells from CD4+ CD25- T cells in UC patients. CONCLUSIONS: The synergistic effects of ER stress and MNP interfere with the development of Tr1 cells. The development of Tr1 from CD4+ CD25- T cells in patients with UC is re-established by Rnf20 inhibition.

Spatial intensity correlations of transmitted intensity patterns emerging from large particles.

Propagation of a coherent light beam through a random medium generates speckle patterns, in which some information of media and object is hidden. Speckles produced by particles smaller than wavelength are studied thoroughly, yet it is also essential to investigate speckles produced by larger particles. In this paper, the spatial intensity correlations of transmitted speckle patterns generated by large particles are studied theoretically and experimentally. A semi-empirical expression of spatial intensity correlation function of speckle patterns is derived based on Bethe-Salpeter equation, taking particle size and concentration into account. After performing experiments with various particle sizes and concentrations, we fit the theoretical expression to experimental results and determine the introduced parameters. We analyze the variation of spatial intensity correlation function with particle size and concentration. Theoretical analyses and experimental results given in this paper have potential applications in coherent imaging through random and disordered media.

5-HT modulates the properties of dendritic cells to interfere with the development of type 1 regulating T cells.

BACKGROUND: 5-hydroxytryptamine (5-HT, serotonin) is a major mediator in allergic reactions. The number of tolerogenic dendritic cell (tolDC) and regulatory T cell is reduced in allergic disorders. The mechanism is unclear. The objective of this study is to elucidate the role of 5-HT in interfering with tolDC generation and regulatory Type 1 T cell (Tr1 cell). METHODS: BALB/c mice were treated with 5-HT-containing nasal instillations. The frequency of tolDC and Tr1 cell was evaluated by flow cytometry. RESULTS: Following treatment with 5-HT nasal instillations for one week, the frequency of tolDC and Tr1 cell was significantly reduced in the respiratory tissues. Higher levels of SOS1 were detected in DCs isolated from the airway tissues of mice treated with 5-HT. A complex of SOS1 and c-Maf was detected in DCs in response to 5-HT stimulation. The expression of IL-10 was suppressed by the presence of 5-HT. The induction of Tr1 cell by DC was substantially compromised by 5-HT. CONCLUSIONS: 5-HT inhibits the expression of IL-10 in DCs. DCs primed with 5-HT lose the ability to induce Tr1 cells.

Galectin-9 in synergy with NF-κB inhibition restores immune regulatory capability in dendritic cells of subjects with food allergy.

The pathogenesis of immune tolerance disruption is not fully understood. Galectin-9 (Gal9) has immune regulatory functions. The objective of the present study is to assess the role of Gal9 in maintaining immune tolerance. Blood and intestinal biopsies were taken from patients with food allergy (FA). The status of tolerogenic dendritic cells (tDC) and type 1 regulatory T cells (Tr1 cells) in the samples was evaluated and used as representative parameters of immune tolerance. An FA mouse model was established to assess the role of Gal9 in maintaining immune tolerance. We found that peripheral CD11c+ CD5+ CD1d+ tDC frequency was significantly lower in FA patients as compared to health control (HC) subjects. There was no significant change in CD11c+ DC frequency between the FA group and the HC group. The expression of IL-10 in peripheral tDCs was lower in the FA group than that in the HC group. A positive correlation was detected between the serum levels of IL-10 and Gal9. The expression of Gal9 was observed in intestinal biopsies, which was positively correlated with the serum levels of Gal9 as well as serum IL-10 levels. Peripheral Tr1 cells had lower frequencies in the FA group than in the non-FA (Con) group. tDCs demonstrated the ability to generate Tr1 cells, which was weaker in the FA group as compared with the Con group. Exposure of FA tDCs to Gal9 in culture restored the ability to generate Tr1 cells. In summary, the lower frequency of tDC and Tr1 cell of FA patients was associated with the levels of Gal9. The presence of Gal9 restored the capacity of tDC to generate Tr1 cells.

5-HT is associated with the dysfunction of regulating T cells in patients with allergic rhinitis.

The dysfunction of regulating T lymphocytes (Treg) is associated with the pathogenesis of many diseases. 5-hydroxytryptamine (5-HT) is capable of interacting with immune cells. The objective of the present study is to shed light on the role of 5-HT in regulating Treg activities. Blood samples were collected from patients with perennial allergic rhinitis (AR). Tregs were isolated from blood samples by magnetic cell sorting. The levels of 5-HT and other cytokines were determined by enzyme-linked immunosorbent assay. The results showed that serum 5-HT levels in patients with AR were higher than in healthy control (HC) subjects. A positive correlation was identified in the data between 5-HT concentrations and AR-related cytokine concentrations in the serum. A negative correlation was found between serum levels of 5-HT and the peripheral frequency of Treg. Exposure to 5-HT enhanced the expression of IL-6 and IL-21 in dendritic cells (DC). Co-culture of 5-HT-primed DCs with Tregs led to the conversion of Th17 cells. STAT3 blockade efficiently abolished the 5-HT-associated conversion of Th17 cells from Tregs. In summary, patients with AR exhibited higher serum concentrations of 5-HT. 5-HT-primed DCs could convert Tregs to Th17 cells.