Curcumin Inhibits T Follicular Helper Cell Differentiation in Mice with Dextran Sulfate Sodium (DSS)-Induced Colitis

Follicular helper T cells (Tfh) regulate the differentiation of germinal center B cells and maintain humoral immunity. Notably, imbalances in Tfh differentiation often lead to the development of autoimmune diseases, including inflammatory bowel disease (IBD). Curcumin, a natural product derived from Curcuma longa, is effective in relieving IBD in humans and animals, and its mechanisms of immune regulation need further elaboration. In this study, dextran sodium sulfate induced ulcerative colitis in BALB/c mice, and curcumin was administered simultaneously for 7 days. Curcumin effectively upregulated the change rate of mouse weight, colonic length, down-regulated colonic weight, index of colonic weight, colonic damage score and the levels of pro-inflammatory cytokines IL-6, IL-12, IL-23 and TGF-[Formula: see text]1 in colonic tissues of colitis mice. Importantly, curcumin regulated the differentiation balance of Tfh and their subpopulation in colitis mice; the percentages of Tfh (CD4[Formula: see text]CXCR5[Formula: see text]BCL-6[Formula: see text], CD4[Formula: see text]CXCR5[Formula: see text]PD-1[Formula: see text], CD4[Formula: see text]CXCR5[Formula: see text]PD-L1[Formula: see text], CD4[Formula: see text]CXCR5[Formula: see text]ICOS[Formula: see text], Tfh17 and Tem-Tfh were downregulated significantly, while CD4[Formula: see text]CXCR5[Formula: see text]Blimp-1[Formula: see text], Tfh1, Tfh10, Tfh21, Tfr, Tcm-Tfh and Tem-GC Tfh were upregulated. In addition, curcumin inhibited the expression of Tfh-related transcription factors BCL-6, p-STAT3, Foxp1, Roquin-1, Roquin-2 and SAP, and significantly upregulated the protein levels of Blimp-1 and STAT3 in colon tissue. In conclusion, curcumin may be effective in alleviating dextran sulfate sodium-induced colitis by regulating Tfh differentiation.

Dysregulated expression of miRNAs in immune thrombocytopenia

In recent years the critical role of miRNAs has been established in many diseases, including autoimmune disorders. Immune thrombocytopenia purpura (ITP) is a predominant autoimmune disease, in which aberrant expression of miRNAs has been observed, suggesting that miRNAs are involved in its development. miRNAs could induce an imbalance in the T helper (Th)1/Th2 cell and Th17/Treg cell-related responses. Moreover, they could also cause alterations in Th9 and Th22 cell responses, and activate Tfh (T follicular helper) cell-dependent auto-reactive B cells, thus influencing megakaryogenesis. Herein, we summarize the role of immune-related miRNAs in ITP pathogenesis, and look forward to clinical applications.

SARS-CoV-2 mRNA vaccination elicits robust and persistent T follicular helper cell response in humans

SummarySARS-CoV-2 mRNA vaccines induce robust anti-spike (S) antibody and CD4+ T cell responses. It is not yet clear whether vaccine-induced follicular helper CD4+ T (TFH) cell responses contribute to this outstanding immunogenicity. Using fine needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we show that frequency of TFH correlates with that of S-binding germinal center B cells. Mining of the responding TFH T cell receptor repertoire revealed a strikingly immunodominant HLADPB1* 04-restricted response to S167-180 in individuals with this allele, which is among the most common HLA alleles in humans. Paired blood and lymph node specimens show that while circulating S-specific TFH cells peak one week after the second immunization, S-specific TFH persist at nearly constant frequencies for at least six months. Collectively, our results underscore the key role that robust TFH cell responses play in establishing long-term immunity by this efficacious human vaccine.

T follicular helper cell expansion and chronic T cell activation are characteristic immune anomalies in Evans syndrome

Pediatric Evans syndrome (pES) is increasingly identified as the presenting manifestation of several inborn errors of immunity (IEI). Despite an improved understanding of genetic defects in pES, the underlying immunobiology of pES is poorly defined, and characteristic diagnostic immune parameters are lacking. We describe the immune characteristics of 24 patients with pES and compared them with 22 patients with chronic immune thrombocytopenia (cITP) and 24 healthy controls (HC). Compared to patients with cITP and HC, patients with pES had increased circulating T-follicular helper cells (cTfh), increased T cell activation, and decreased naïve CD4+ T cells for age. Despite normal or high IgG in the majority of pES at presentation, class-switched memory B cells (CSMB) were decreased. Within the cTfh subset, we noted features of post-activation exhaustion with upregulation of several canonical checkpoint inhibitors. TCR-b repertoire analysis of cTfh cells revealed increased oligoclonality in patients with pES compared with HC. Among patients with pES, those without a known gene defect had a similar characteristic immune abnormality as patients with defined genetic defects. Similarly, patients with pES with normal IgG had similar T cell abnormalities as patients with low IgG. Since genetic defects have been identified in only less than half of patients with pES, our findings of similar immune abnormalities across all pES patients help establish a common characteristic immunopathology in pES irrespective of the underlying genetic etiology.