Pemphigus is a skin and mucosal membrane-targeting autoimmune bullous disease. Previous studies have shown that circulating anti-desmoglein1/3 antibodies are pathogenic and mediate blister formation. However, the role of infiltrating immune cells in lesional skin has not been fully investigated. In this study we showed that there existed a large number of B and T lymphocytes and plasma cells in the skin lesions by immunohistochemistry and immunofluorescence staining. In addition, a significantly increased number of Dsg1- and Dsg3-specific B cells could be identified by flow cytometric analysis or enzyme-linked immunospot technique (i.e., ELISPOT) assay. Furthermore, anti-Dsg1 and Dsg3 antibodies could be detected from the supernatant of in vitro cultures with isolated lymphocytes from lesional skin. We found that most T lymphocytes infiltrating pemphigus vulgaris lesions were CD4 T helper cells expressing IL-21 and IL-17a but not typical T follicular helper cells expressing CXCR5. Additionally, our microarray assay showed that the level of chemokine CCL19 was significantly elevated, suggesting active T-/B-lymphocyte trafficking and aggregation in the pemphigus vulgaris lesions. Collectively, our results suggest a critical role of locally infiltrating lymphocytes in pemphigus pathogenesis.

A deeper understanding of the immunological events during pregnancy will provide novel insights into the pathogenesis of pregnancy complications. The fundamental function of T follicular helper (Tfh) cells is to provide cognate help to B cells. Dysregulations of Tfh-cell function and/or development can result in various immunological diseases. However, the role and characteristics of Tfh cells during pregnancy remain unknown. Herein, an allogeneic-normal-pregnant mouse model was used, and we found that the CD4+ T cells residing at the uterus and placenta (UP) displayed a Tfh-like phenotype; and the UP-derived CD4+CXCR5hiPD-1hi and CD4+CXCR5hiICOShi Tfh cells, which showed a memory/activation phenotype, reached their peak at mid-pregnancy. These Tfh cells were located abundantly in the uterus at mid-pregnancy, but greatly increased in the placenta at late-pregnancy. Furthermore, increased foetal resorption by PDL1 blockade correlated with enhanced accumulation of Tfh cells and upregulated expressions of ICOS and PD-1 on these cells. Collectively, our findings are the first to indicate that an adequate and balanced accumulation of Tfh cells during gestation is likely to help maintaining a successful pregnancy, whereas an excessively high level of these cells could lead to abortion.

Decidual CD4+ T (dCD4 T) cells are crucial for the maternal-fetal immune tolerance required for a healthy pregnancy outcome. However, their molecular and functional characteristics are not well elucidated. In this study, we performed the first analysis of transcriptional and alternative splicing (AS) landscapes for paired decidual and peripheral blood CD4+ T (pCD4 T) cells in human early pregnancy using high throughput mRNA sequencing. Our data showed that dCD4 T cells are endowed with a unique transcriptional signature when compared to pCD4 T cells: dCD4 T cells upregulate 1,695 genes enriched in immune system process whereas downregulate 1,011 genes mainly related to mRNA catabolic process and the ribosome. Moreover, dCD4 T cells were observed to be at M phase, and show increased activation, proliferation, and cytokine production, as well as display an effector-memory phenotype and a heterogenous nature containing Th1, Th17, and Treg cell subsets. However, dCD4 T cells undergo a comparable number of upregulated and downregulated AS events, both of which are enriched in the genes related to cellular metabolic process. And the changes at the AS event level do not reflect measurable differences at the gene expression level in dCD4 T cells. Collectively, our findings provide a comprehensive portrait of the unique transcriptional signature and AS profile of CD4+ T cells in human decidua and help us gain more understanding of the functional characteristic of these cells during early pregnancy.

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