IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo

M M Fort; J Cheung; D Yen; J Li; S M Zurawski; S Lo; S Menon; T Clifford; B Hunte; R Lesley; T Muchamuel; S D Hurst; G Zurawski; M W Leach; D M Gorman; D M Rennick

doi:10.1016/s1074-7613(01)00243-6

IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo

Immunity. 2001 Dec;15(6):985-95. doi: 10.1016/s1074-7613(01)00243-6.

Authors

M M Fort¹, J Cheung, D Yen, J Li, S M Zurawski, S Lo, S Menon, T Clifford, B Hunte, R Lesley, T Muchamuel, S D Hurst, G Zurawski, M W Leach, D M Gorman, D M Rennick

Affiliation

¹ DNAX Research Institute, Palo Alto, CA 94304, USA.

PMID: 11754819
DOI: 10.1016/s1074-7613(01)00243-6

Abstract

We have characterized a cytokine produced by Th2 cells, designated as IL-25. Infusion of mice with IL-25 induced IL-4, IL-5, and IL-13 gene expression. The induction of these cytokines resulted in Th2-like responses marked by increased serum IgE, IgG(1), and IgA levels, blood eosinophilia, and pathological changes in the lungs and digestive tract that included eosinophilic infiltrates, increased mucus production, and epithelial cell hyperplasia/hypertrophy. In addition, our studies show that IL-25 induces Th2-type cytokine production by accessory cells that are MHC class II(high), CD11c(dull), and lineage(-). These results suggest that IL-25, derived from Th2 T cells, is capable of amplifying allergic type inflammatory responses by its actions on other cell types.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Cell Lineage
Cells, Cultured
Cloning, Molecular
DNA-Binding Proteins / deficiency
DNA-Binding Proteins / genetics
Eosinophilia / chemically induced*
Eosinophilia / immunology
Eosinophilia / pathology
Gastric Mucosa / pathology
Gastrointestinal Diseases / chemically induced*
Gastrointestinal Diseases / immunology
Gastrointestinal Diseases / pathology
Gene Expression Regulation / drug effects*
Growth Substances / isolation & purification*
Growth Substances / metabolism
Growth Substances / pharmacology
Growth Substances / toxicity
Histocompatibility Antigens Class II / analysis
Humans
Hypergammaglobulinemia / chemically induced*
Hyperplasia
Hypertrophy
Integrin alphaXbeta2 / analysis
Interleukin-13 / biosynthesis*
Interleukin-13 / genetics
Interleukin-17
Interleukin-4 / biosynthesis*
Interleukin-4 / genetics
Interleukin-5 / biosynthesis*
Interleukin-5 / genetics
Interleukins*
Intestinal Mucosa / pathology
Lung / pathology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Molecular Sequence Data
Nuclear Proteins
Pulmonary Eosinophilia / chemically induced
Pulmonary Eosinophilia / immunology
Pulmonary Eosinophilia / pathology
RNA, Messenger / biosynthesis
Receptors, Interleukin-4 / deficiency
Receptors, Interleukin-4 / genetics
Sequence Alignment
Sequence Homology, Amino Acid
T-Lymphocyte Subsets / drug effects*
T-Lymphocyte Subsets / metabolism
Th2 Cells / chemistry
Th2 Cells / metabolism*

Substances

DNA-Binding Proteins
Growth Substances
Histocompatibility Antigens Class II
IL25 protein, human
Integrin alphaXbeta2
Interleukin-13
Interleukin-17
Interleukin-5
Interleukins
Mydgf protein, mouse
Nuclear Proteins
RAG2 protein, human
RNA, Messenger
Rag2 protein, mouse
Receptors, Interleukin-4
V(D)J recombination activating protein 2
Interleukin-4