NOD2 regulates hematopoietic cell function during graft-versus-host disease.
Nucleotide-binding oligomerization domain 2 (NOD2) polymorphisms are independent risk factors for Crohn's disease and graft-versus-host disease (GVHD). In Crohn's disease, the proinflammatory state resulting from NOD2 mutations have been associated with a loss of antibacterial function of enterocytes such as paneth cells. NOD2 has not been studied in experimental allogeneic bone marrow transplantation (allo-BMT). Using chimeric recipients with NOD2(-/-) hematopoietic cells, we demonstrate that NOD2 deficiency in host hematopoietic cells exacerbates GVHD. We found that proliferation and activation of donor T cells was enhanced in NOD-deficient allo-BMT recipients, suggesting that NOD2 plays a role in the regulation of host antigen-presenting cells (APCs). Next, we used bone marrow chimeras in an experimental colitis model and observed again that NOD2 deficiency in the hematopoietic cells results in increased intestinal inflammation. We conclude that NOD2 regulates the development of GVHD through its inhibitory effect on host APC function.
Penack
Olaf
O
Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Smith
Odette M
OM
Cunningham-Bussel
Amy
A
Liu
Xin
X
Rao
Uttam
U
Yim
Nury
N
Na
Il-Kang
IK
Holland
Amanda M
AM
Ghosh
Arnab
A
Lu
Sydney X
SX
Jenq
Robert R
RR
Liu
Chen
C
Murphy
George F
GF
Brandl
Katharina
K
van den Brink
Marcel R M
MR
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000276:immunology; D003092:Colitis / Q000209:etiology; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology; D006413:Hematopoietic System / Q000166:cytology / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D009374:Neoplasms, Experimental / Q000276:immunology; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide
D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse