IL-7 deficiency prevents development of a non-T cell non-B cell-mediated colitis.
IL-7 is a stromal cell-derived cytokine with a well-established physiologic role in lymphocyte biology. This report describes an unexpected role for IL-7 in the development of colitis in a T and B cell-deficient environment. Recombination-activating gene-2 (RAG-2)-deficient mice (RAG-2(-/-)) were exposed to and subsequently maintained a horizontally transmitted microbial flora that included Helicobacter hepaticus. These animals mounted a strong myeloid cell response and developed both systemic and local signs of a severe colitis. A striking infiltration of F4/80 and MHC class II-positive cells was seen in the colon and cecum of animals undergoing the disease. Mice mutant for both IL-7 and RAG-2 (IL-7/RAG-2(-/-)) that were colonized by the same flora showed no signs of myeloid responses or colitis, indicating that IL-7 plays a critical role in exacerbating a non-T cell/non-B cell-mediated chronic inflammatory response. Recombinant IL-10 protein therapy was able to prevent the occurrence of colitis in susceptible mice, suggesting a pivotal role for macrophages. The implications of a role for IL-7 in this disease model with respect to human inflammatory bowel disease are discussed.
von Freeden-Jeffry
U
U
Department of Immunobiology, DNAX Research Institute, Palo Alto, CA 94304, USA.
Davidson
N
N
Wiler
R
R
Fort
M
M
Burdach
S
S
Murray
R
R
D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000473:pathology*; D002465:Cell Movement / Q000276:immunology; D003092:Colitis / Q000235:genetics* / Q000276:immunology* / Q000517:prevention & control; D004268:DNA-Binding Proteins / Q000235:genetics; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D016481:Helicobacter Infections / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D007111:Immunity, Cellular / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics / Q000627:therapeutic use; D015851:Interleukin-7 / Q000172:deficiency* / Q000235:genetics*; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000473:pathology*
D004268:DNA-Binding Proteins; D015851:Interleukin-7; C499308:Rag2 protein, mouse; D011994:Recombinant Proteins; C064655:V(D)J recombination activating protein 2; D016753:Interleukin-10