(Cell Reports 29, 1848–1861.e1–e6; November 12, 2019) In the originally published version of this article, the order of equal contributors was incorrect. The correct order is: Erxia Shen, Hardis Rabe, Lin Luo, Lei Wang. The authors regret this error. Control of Germinal Center Localization and Lineage Stability of Follicular Regulatory T Cells by the Blimp1 Transcription FactorShen et al.Cell ReportsNovember 12, 2019In BriefShen et al. identify Blimp1 as a critical transcription factor for the proper positioning and stable expression of the suppressive activity of TFR cells that control GC responses. In the absence of Blimp1, unstable TFR cells prematurely migrate into the GC and differentiate into TFH-like cells to promote dysregulated GC responses. Full-Text PDF Open Access
T cell-dependent B-cell responses decline with age, indicating declined cognate helper activity of aged CD4 + T cells for B cells. However, the mechanisms remain unclear. T follicular helper (Tfh) cells, a novel T helper subset, play an essential role in helping B cells differentiation into long-lived plasma cells in germinal center (GC) or short-lived plasma cells. In the present study, we proposed that there might existe changes of proportion, phenotype or cytokine production of blood Tfh cells in healthy elderly individuals compared with healthy young individuals.The results showed that frequencies of aged blood CXCR5 + CD4 + Tfh cells increased compared with young subjects. Both aged and young blood CXCR5 + CD4 + Tfh cells constitutively expressed CD45RO, CCR7 and CD28, and few of these cells expressed CD69 or HLA-DR, which indicated that they were resting memory cells. There was no significant difference of IL-21 frequency production by aged blood CXCR5 + CD4 + Tfh determined by FACS compared with young individuals, however, aged PBMCs produced significantly higher levels of IL-21 evaluated by ELISA. Furthermore, there were no significant differences of percentages of IFN-γ, IL-4, IL-17 or IL-22 production by aged Tfh cells compared with their counterparts of young individuals respectively. However, frequencies of IL-17+ cells within aged CD4 + CXCR5-T cells were markedly lower than in the young individuals. Furthermore we observed different frequencies of IFN-γ, IL-17, IL-4 or IL-22 production by Tfh or by CD4 + CXCR5- cells in aged and young subjects respectively.Our data demonstrated that the frequencies of blood memory CXCR5 + CD4 + Tfh cells increased in the elderly population. There were similar frequencies of Th characterized cytokine production such as IL-21, IFN-γ, IL-4, IL-17 or IL-22 in aged and young Tfh cells. However, aged PBMCs produced a significantly higher amount of IL-21 compare to young subjects.
TLRs are involved in the regulation of immune responses. R-848, a TLR7/8 ligand, has potent anti-viral and anti-tumour properties and has been used as a new immune response modifier for enhancing Th1 immune response. In this study, we found that R-848 significantly inhibited IgE synthesis from murine B cells at the single cell levels by anti-CD40 plus IL-4-stimulated splenocytes, in which R-848 acted on the early stage of B cell differentiation to modulate IgE synthesis. This inhibitory effect of R-848 on IgE synthesis was not isotype specific as it also inhibited IgG1 synthesis. Moreover, R-848 had no significant effect on the production of IgG2a by anti-CD40 plus IL-4-stimulated splenocytes. Further studies showed that R-848 markedly promoted murine B cell activation induced by anti-CD40 plus IL-4 by up-regulating the expression of B cell activation markers CD25, CD69 and co-stimulatory molecule CD80. In contrast, R-848 inhibited the proliferation and division of murine B cells in anti-CD40 plus IL-4-stimulated splenocytes. R-848 promoted the production of IFN-gamma and IL-12 that were partially responsible for its inhibitory effect on IgE production by anti-CD40 plus IL-4 because the addition of anti-IFN-gamma or anti-IL-12 mAbs to the cultures could significantly restore IgE production by splenocytes. Importantly, R-848 had a direct effect on purified B cells to inhibit IgE production induced by anti-CD40 plus IL-4. Taken together, these results demonstrate that R-848 markedly inhibits IgE synthesis, and suggest that R-848 could be used to treat allergic diseases.
To compare the phenotype and cytokines expression in CD4~(+)CD25~(+)T and CD4~(+)CD25~(-)T cells,single cell suspensions from mouse spleen were prepared and the CD4~(+)、CD4~(+)CD25~(+)、CD4~(+)CD25~(-)T cells were isolated.The expression of surface molecules,transcriptional factors and cytokines was determined and analysed at the single cell level by FACS.It was found that 7.8% of CD4~(+)T cells expressed CD25.Compared with CD4~(+)CD25~(-)T cells,expression of CD44 on CD4~(+)CD25~(+)T cells increased slightly,CD45RB decreased remarkably,CTLA-4 and Foxp3 increased significantly.The majority of CD4~(+)CD25~(+)T cells expressed both CTLA-4 and Foxp3,and much less cells expressed Foxp3 alone.The results of intracellular cytokines staining indicated that the frequency of IL-2~(+) and IFN-γ~(+) CD4~(+)CD25~(+)T cells decreased remarkably,and the frequency of IL-10~(+) CD4~(+)CD25~(+)T cells increased lightly compared with CD4~(+)CD25~(-)T cells.It is evident that the CD4~(+)CD25~(+)regulatory T cells differs both in the phenotype and the expressions of transcriptional factors and cytokines,with the CD4~(+)CD25~(-) non-regulatory T cells cells.It was different in phenotype、expression of transcriptional factors and cytokines in CD4~(+)CD25~(+)T cells and CD4~(+)CD25~(-)T cells.
Psoriasis is a chronic autoimmune inflammatory disease that remains active for a long period, even for life in most patients. The impact of psoriasis on health is not only limited to the skin, but also influences multiple systems of the body, even mental health. With the increasing of literature on the association between psoriasis and extracutaneous systems, a better understanding of psoriasis as an autoimmune disease with systemic inflammation is created. Except for cardiometabolic diseases, gastrointestinal diseases, chronic kidney diseases, malignancy, and infections that have received much attention, the association between psoriasis and more systemic diseases, including the skin system, reproductive system, and oral and ocular systems has also been revealed, and mental health diseases draw more attention not just because of the negative mental and mood influence caused by skin lesions, but a common immune-inflammatory mechanism identified of the two systemic diseases. This review summarizes the epidemiological evidence supporting the association between psoriasis and important and/or newly reported systemic diseases in the past 5 years, and may help to comprehensively recognize the comorbidity burden related to psoriasis, further to improve the management of people with psoriasis.
Children are prone to get infections, especially in the respiratory system and the gut mainly because their immune system is immature. T cells significantly contribute to the prevention of infections, and different helper T cell (Th) subsets play different anti-pathogen roles. Interleukin (IL)-22 producing by T-helper 22 cells (Th22) play an important role in host defense against Gram-negative bacterial organisms in gut and lung. T-helper 17 cells (Th17) protect against extracelluar bacteria and fungi especially at the epithelial surface. However, there is no report comparing IL-22 producing T cells and Th17 cells in healthy young children to adults. Flow cytometry (FCM) was used to observe whether Th22 subset existed in the peripheral blood of healthy young children. Meanwhile, we determined the frequencies of Th subsets including Th17, Th1 and Th2, cytotoxic T (Tc)1 subset, CD4+ and CD8+ memory T cells in the peripheral blood of both young children and adults. In the present study, we demonstrated that Th22 subset existed in peripheral blood of children, with IL-22 mainly secreted by CD4 + CD45RO+ memory T cells. Moreover, we observed that IL-22 + CD4 + T cells and Th subsets including Th17, Th1, and Th2 frequencies of young children (1–6 years old) were significantly lower than adults. While the Th1 frequency from Group A (1–3 years old) was markedly lower than that from Group B (4–6 years old). No significant differences of Th17 or IL-22 + CD4 + T cells frequencies were observed between these two groups. In addition, Tc1 subset frequencies were also remarkably lower in young children than in adults. Furthermore, lower frequencies of CD45RO+ memory CD4+ and CD8+ T cells in young children than in adults, and significant correlation between CD45RO+ memory CD4 + T cells and IL-22 + CD4 + T cells, Th1, Th17 were observed. Th22 subset exists in the peripheral blood of young children. Compared with adults, there are lower frequencies of IL-22 + CD4 + T cells, as well as Th1, Th17, Th2 and Tc1 subsets in the peripheral blood of young children.
Objective To evaluate whether depletion of CD4 + CD25 + T cells leads to increased humoral immune response of mice immunized with OVA. Methods Groups of mice received one i.p. injection of anti-CD25 mAb, 3、10、27 days later, blood was harvested and the percentage of CD4 + CD25 + T cells was determined by FACS. 3 days after injection of anti-CD25 mAb, depleted and un-deplleted CD4 + CD25 + T cells mice were immunized with OVA + ALUM, and boosted 7 days later. Blood was harvested from mice 7 days after prime and 14 days after boost, and OVA specific IgE and IgG1 in sera were determined by ELISA. Results 3 days and 10 days after injection of anti-CD25 mAb, there were no CD4 + CD25 + T cells in blood; 27 days after injection of anti-CD25 mAb, there were CD4 + CD25 + T cells of which percentage was lower than normal mice. 7 days after prime, depletion of CD4 + CD25 + T cells leaded to increased total IgE, OVA specific IgE and IgG1; 14 days after boost, depletion of CD4 + CD25 + T cells leaded to increased OVA specific IgE. Conclusion Depletion of CD4 + CD25 + T cells could effect OVA specific humoral immune response of mice immunized with OVA.
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