CMRF-35 mAb cross-regulates IFN-α and TNF-α production by pDCs. (A) pDC stimulation with TLR7 ligand ssRNA or TLR9 ligand CpG DNA induces type I interferon and TNF-α secretion (1). Overproduction of TNF-α inhibits secretion of type I interferon (2), whereas a certain level of type I interferon sustains pDC TNF-α production level (3), thus maintaining the balance of type I interferon and TNF-α secretion on pDCs. High levels of type I interferon down-regulate CD300a/c on pDCs (4), indicating regulation of the immunoregulatory molecules in a feedback loop. (B) Cross-linking pDCs with CMRF-35 mAb, which recognizes both CD300a and CD300c, increases IRF7 expression and the secretion of type I interferon (5) and down-regulates TNF-α production (6), indicating the potential of these molecules to be powerful modulators of immune reactions.