| First Author | Katakam AK | Year | 2015 |
| Journal | Proc Natl Acad Sci U S A | Volume | 112 |
| Issue | 47 | Pages | 14664-9 |
| PubMed ID | 26561586 | Mgi Jnum | J:228057 |
| Mgi Id | MGI:5705165 | Doi | 10.1073/pnas.1520627112 |
| Citation | Katakam AK, et al. (2015) Dendritic cells require NIK for CD40-dependent cross-priming of CD8+ T cells. Proc Natl Acad Sci U S A 112(47):14664-9 |
| abstractText | Dendritic cells (DCs) link innate and adaptive immunity and use a host of innate immune and inflammatory receptors to respond to pathogens and inflammatory stimuli. Although DC maturation via canonical NF-kappaB signaling is critical for many of these functions, the role of noncanonical NF-kappaB signaling via the serine/threonine kinase NIK (NF-kappaB-inducing kinase) remains unclear. Because NIK-deficient mice lack secondary lymphoid organs, we generated transgenic mice with targeted NIK deletion in CD11c(+) cells. Although these mice exhibited normal lymphoid organs, they were defective in cross-priming naive CD8(+) T cells following vaccination, even in the presence of anti-CD40 or polyinosinic:polycytidylic acid to induce DC maturation. This impairment reflected two intrinsic defects observed in splenic CD8(+) DCs in vitro, namely antigen cross-presentation to CD8(+) T cells and secretion of IL-12p40, a cytokine known to promote cross-priming in vivo. In contrast, antigen presentation to CD4(+) T cells was not affected. These findings reveal that NIK, and thus probably the noncanonical NF-kappaB pathway, is critical to allow DCs to acquire the capacity to cross-present antigen and prime CD8 T cells after exposure to licensing stimuli, such as an agonistic anti-CD40 antibody or Toll-like receptor 3 ligand. |
