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MicroRNAs (miRNAs) are important regulators of cell fate decisions in immune responses. They act by coordinate repression of multiple target genes, a property that we exploited to uncover regulatory networks that govern T helper-2 (Th2) cells. A functional screen of individual miRNAs in primary T cells uncovered multiple miRNAs that inhibited Th2 cell differentiation. Among these were miR-24 and miR-27,...
During persistent antigen stimulation, CD8+ T cells show a gradual decrease in effector function, referred to as exhaustion, which impairs responses in the setting of tumors and infections. Here we demonstrate that the transcription factor NFAT controls the program of T cell exhaustion. When expressed in cells, an engineered form of NFAT1 unable to interact with AP-1 transcription factors diminished...
T follicular helper (Tfh) cells provide help to B cells and are crucial for establishment of germinal center (GC) reactions, including production of high-affinity antibodies and generation of memory B cells and long-lived plasma cells. Here we report that the magnitude of the Tfh cell response was dictated by the amount of antigen and directly correlated with the magnitude of the GC B cell response...
Follicular helper T cells (Tfh cells) are the major producers of interleukin-4 (IL-4) in secondary lymphoid organs where humoral immune responses develop. Il4 regulation in Tfh cells appears distinct from the classical T helper 2 (Th2) cell pathway, but the underlying molecular mechanisms remain largely unknown. We found that hypersensitivity site V (HS V; also known as CNS2), a 3′ enhancer in the...
MicroRNA (miRNA)-deficient helper T cells exhibit abnormal IFN-γ production and decreased proliferation. However, the contributions of individual miRNAs to this phenotype remain poorly understood. We conducted a screen for miRNA function in primary T cells and identified individual miRNAs that rescue the defects associated with miRNA deficiency. Multiple members of the miR-17 and miR-92 families enhanced...
The factors regulating dendritic cell (DC) development and homeostasis are incompletely understood. Here, we demonstrate that DCs express the lymphotoxin (LT)-β receptor (LTβR) and that in mice lacking the LTβR in hematopoietic cells, spleen, and lymph node, CD8 − DC numbers are reduced. B cells are a key source of LTα1β2 for splenic DC homeostasis, and transgenic overexpression of LTα1β2...
B1 cells are a predominant cell type in body cavities and an important source of natural antibody. Here we report that in mice lacking the chemokine, CXCL13, B1 cells are deficient in peritoneal and pleural cavities but not in spleen. CXCL13 is produced by cells in the omentum and by peritoneal macrophages, and in adoptive transfers, B1 cells home to the omentum and the peritoneal cavity in a CXCL13-dependent...
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