Pro-inflammatory NK-like T cells are expanded in the blood and inflamed intestine in Crohn's disease.

Altered intestinal immune homeostasis leads to chronic inflammation in Crohn's disease (CD). To address disease- and tissue-specific alterations, we performed a T cell-centric mass cytometry analysis of peripheral and intestinal lymphocytes from patients with CD and healthy donors' PBMCs. Chronic intestinal inflammation enforced activation, exhaustion, and terminal differentiation of CD4 and CD8 T cells and a relative enrichment of CD4 regulatory T (Treg) cells.

Oligoclonal CD4CXCR5 T cells with a cytotoxic phenotype appear in tonsils and blood.

In clinical situations, peripheral blood accessible CD3CD4CXCR5 T-follicular helper (T) cells may have to serve as a surrogate indicator for dysregulated germinal center responses in tissues. To determine the heterogeneity of T cells in peripheral blood versus tonsils, CD3CD4CD45RACXCR5 cells of both origins were sorted. Transcriptomes, TCR repertoires and cell-surface protein expression were analysed by single-cell RNA sequencing, flow cytometry and immunohistochemistry.

Bactericidal/permeability-increasing protein instructs dendritic cells to elicit Th22 cell response.

Neutrophil-derived bactericidal/permeability-increasing protein (BPI) is known for its bactericidal activity against gram-negative bacteria and neutralization of lipopolysaccharide. Here, we define BPI as a potent activator of murine dendritic cells (DCs). As shown in GM-CSF-cultured, bone-marrow-derived cells (BMDCs), BPI induces a distinct stimulation profile including IL-2, IL-6, and tumor necrosis factor expression.

NFAT signaling is indispensable for persistent memory responses of MCMV-specific CD8+ T cells.

Cytomegalovirus (CMV) induces a unique T cell response, where antigen-specific populations do not contract, but rather inflate during viral latency. It has been proposed that subclinical episodes of virus reactivation feed the inflation of CMV-specific memory cells by intermittently engaging T cell receptors (TCRs), but evidence of TCR engagement has remained lacking. Nuclear factor of activated T cells (NFAT) is a family of transcription factors, where NFATc1 and NFATc2 signal downstream of TCR in mature T lymphocytes.

Delayed and limited administration of the JAKinib tofacitinib mitigates chronic DSS-induced colitis.

In inflammatory bowel disease, dysregulated T cells express pro-inflammatory cytokines. Using a chronic azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis model resembling ulcerative colitis, we evaluated whether and when treatment with the Janus kinase (JAK) inhibitor tofacitinib could be curative. Comparing the treatment with two and three cycles of tofacitinib medication in drinking water - intermittently with DSS induction - revealed that two cycles were not only sufficient but also superior over the 3-x regimen.