PMID- 26561586
OWN - NLM
STAT- MEDLINE
DCOM- 20160317
LR  - 20231213
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 112
IP  - 47
DP  - 2015 Nov 24
TI  - Dendritic cells require NIK for CD40-dependent cross-priming of CD8+ T cells.
PG  - 14664-9
LID - 10.1073/pnas.1520627112 [doi]
AB  - 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.
FAU - Katakam, Anand K
AU  - Katakam AK
AD  - Department of Pathology, Genentech Inc., South San Francisco, CA 94080;
FAU - Brightbill, Hans
AU  - Brightbill H
AD  - Department of Immunology, Genentech Inc., South San Francisco, CA 94080;
FAU - Franci, Christian
AU  - Franci C
AD  - Department of Cancer Immunology, Genentech Inc., South San Francisco, CA 94080;
FAU - Kung, Chung
AU  - Kung C
AD  - Department of Mouse Genetics, Genentech Inc., South San Francisco, CA 94080.
FAU - Nunez, Victor
AU  - Nunez V
AD  - Department of Pathology, Genentech Inc., South San Francisco, CA 94080;
FAU - Jones, Charles 3rd
AU  - Jones C 3rd
AD  - Department of Pathology, Genentech Inc., South San Francisco, CA 94080;
FAU - Peng, Ivan
AU  - Peng I
AD  - Department of Immunology, Genentech Inc., South San Francisco, CA 94080;
FAU - Jeet, Surinder
AU  - Jeet S
AD  - Department of Immunology, Genentech Inc., South San Francisco, CA 94080;
FAU - Wu, Lawren C
AU  - Wu LC
AD  - Department of Immunology, Genentech Inc., South San Francisco, CA 94080;
FAU - Mellman, Ira
AU  - Mellman I
AD  - Department of Cancer Immunology, Genentech Inc., South San Francisco, CA 94080; 
      mellman.ira@gene.com caustin@gene.com.
FAU - Delamarre, Lelia
AU  - Delamarre L
AD  - Department of Cancer Immunology, Genentech Inc., South San Francisco, CA 94080;
FAU - Austin, Cary D
AU  - Austin CD
AD  - Department of Pathology, Genentech Inc., South San Francisco, CA 94080; 
      mellman.ira@gene.com caustin@gene.com.
LA  - eng
PT  - Journal Article
DEP - 20151111
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (CD11c Antigen)
RN  - 0 (CD40 Antigens)
RN  - 0 (Interleukin-12 Subunit p40)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.7.- (Cre recombinase)
RN  - EC 2.7.7.- (Integrases)
SB  - IM
MH  - Animals
MH  - Antigen Presentation/immunology
MH  - CD11c Antigen/metabolism
MH  - CD40 Antigens/*metabolism
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cross-Priming/*immunology
MH  - Dendritic Cells/*metabolism
MH  - Gene Deletion
MH  - Integrases/metabolism
MH  - Interleukin-12 Subunit p40/metabolism
MH  - Mice, Transgenic
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Spleen/cytology
MH  - NF-kappaB-Inducing Kinase
PMC - PMC4664370
OTO - NOTNLM
OT  - CD8 T cells
OT  - NIK
OT  - antigen cross-presentation
OT  - cross-priming
OT  - dendritic cells
COIS- The authors declare no conflict of interest.
EDAT- 2015/11/13 06:00
MHDA- 2016/03/18 06:00
PMCR- 2016/05/24
CRDT- 2015/11/13 06:00
PHST- 2015/11/13 06:00 [entrez]
PHST- 2015/11/13 06:00 [pubmed]
PHST- 2016/03/18 06:00 [medline]
PHST- 2016/05/24 00:00 [pmc-release]
AID - 1520627112 [pii]
AID - 201520627 [pii]
AID - 10.1073/pnas.1520627112 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2015 Nov 24;112(47):14664-9. doi: 
      10.1073/pnas.1520627112. Epub 2015 Nov 11.