The R1-5D9 antibody reacts with mouse IL-12. IL-12 is a heterodimeric cytokine composed of subunits IL-12α p35 and IL-12β p40. IL-12 is secreted by activated monocytes, macrophages, and dendritic cells. IL-12 plays roles in T lymphocyte differentiation, IFNγ production, and NK cell cytotoxicity. Overexpression of IL-12 p40 was observed in the central nervous system of patients with multiple sclerosis, suggesting a role of this cytokine in the pathogenesis of the disease.

INVIVOMAB ANTI-MOUSE IL-12 P40 (CLONE: R1-5D9)

 

Choi, Y. S., et al. (2015). “LEF-1 and TCF-1 orchestrate TFH differentiation by regulating differentiation circuits upstream of the transcriptional repressor Bcl6.” Nat Immunol 16(9): 980-990. PubMed

Follicular helper T cells (TFH cells) are specialized effector CD4(+) T cells that help B cells develop germinal centers (GCs) and memory. However, the transcription factors that regulate the differentiation of TFH cells remain incompletely understood. Here we report that selective loss of Lef1 or Tcf7 (which encode the transcription factor LEF-1 or TCF-1, respectively) resulted in TFH cell defects, while deletion of both Lef1 and Tcf7 severely impaired the differentiation of TFH cells and the formation of GCs. Forced expression of LEF-1 enhanced TFH differentiation. LEF-1 and TCF-1 coordinated such differentiation by two general mechanisms. First, they established the responsiveness of naive CD4(+) T cells to TFH cell signals. Second, they promoted early TFH differentiation via the multipronged approach of sustaining expression of the cytokine receptors IL-6Ralpha and gp130, enhancing expression of the costimulatory receptor ICOS and promoting expression of the transcriptional repressor Bcl6.

 

Bertin, S., et al. (2014). “The ion channel TRPV1 regulates the activation and proinflammatory properties of CD4(+) T cells.” Nat Immunol 15(11): 1055-1063. PubMed

TRPV1 is a Ca(2+)-permeable channel studied mostly as a pain receptor in sensory neurons. However, its role in other cell types is poorly understood. Here we found that TRPV1 was functionally expressed in CD4(+) T cells, where it acted as a non-store-operated Ca(2+) channel and contributed to T cell antigen receptor (TCR)-induced Ca(2+) influx, TCR signaling and T cell activation. In models of T cell-mediated colitis, TRPV1 promoted colitogenic T cell responses and intestinal inflammation. Furthermore, genetic and pharmacological inhibition of TRPV1 in human CD4(+) T cells recapitulated the phenotype of mouse Trpv1(-/-) CD4(+) T cells. Our findings suggest that inhibition of TRPV1 could represent a new therapeutic strategy for restraining proinflammatory T cell responses.