RIP2 contributes to Nod signaling but is not essential for T cell proliferation, T helper differentiation or TLR responses.
Receptor-interacting protein 2 (RIP2), also known as CARDIAK and RICK, has been reported to play a role in both adaptive T cell responses and innate immunity as a mediator in TLR signaling and nucleotide-binding oligomerization domain (Nod) signaling. Because initial reports remain controversial, we have further examined both innate and adaptive immune responses in RIP2-deficient mice on the C57BL/6 background. Despite the up-regulation of RIP2 after T cell activation, we could not detect any defect in T cell proliferation or Th1/Th2 responses in RIP2-KO mice. Furthermore, we found that TLR responses in RIP2-deficient macrophages were normal. However, our analysis showed that Nod signaling was impaired in macrophages from RIP2-deficient mice. In conclusion, our data demonstrate a critical role for RIP2 in Nod signaling, while T cell proliferation, T helper differentiation and TLR responses were unaffected by the absence of RIP2.
Hall
Håkan T L
HT
Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Department of Immunology, University of Toronto, Toronto, Canada.
Wilhelm
Margareta T
MT
Saibil
Samuel D
SD
Mak
Tak W
TW
Flavell
Richard A
RA
Ohashi
Pamela S
PS
D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053472:Nod Signaling Adaptor Proteins / Q000276:immunology* / Q000378:metabolism; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D053472:Nod Signaling Adaptor Proteins; D051193:Toll-Like Receptors; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506255:Ripk2 protein, mouse