Global Gene Expression Profiles During Acute Pathogen-Induced Pulmonary Inflammation Reveal Divergent Roles for Th1 and Th2 Responses in Tissue Repair

• Published in: The Journal of immunology (1950) Vol. 171; no. 7; pp. 3655 - 3667
• Main Authors: Sandler, Netanya G, Mentink-Kane, Margaret M, Cheever, Allen W, Wynn, Thomas A
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-10-2003
• Subjects: Acute Disease; Animals; Antigens, Helminth - administration & dosage; Antigens, Helminth - immunology; Cells, Cultured; Chitinases - biosynthesis; Chitinases - genetics; Cytokines - biosynthesis; Extracellular Matrix Proteins - biosynthesis; Extracellular Matrix Proteins - genetics; Gene Expression Profiling - methods; Immunophenotyping; Lung Diseases, Parasitic - genetics; Lung Diseases, Parasitic - immunology; Lung Diseases, Parasitic - pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Oligonucleotide Array Sequence Analysis - methods; Ovum - immunology; Schistosoma mansoni - immunology; Schistosomiasis mansoni - genetics; Schistosomiasis mansoni - immunology; Schistosomiasis mansoni - pathology; Species Specificity; Th1 Cells - enzymology; Th1 Cells - immunology; Th1 Cells - metabolism; Th1 Cells - parasitology; Th2 Cells - enzymology; Th2 Cells - immunology; Th2 Cells - metabolism; Th2 Cells - parasitology; Up-Regulation - genetics; Up-Regulation - immunology; Wound Healing - genetics; Wound Healing - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.171.7.3655

T helper 1 responses are typically proinflammatory, while Th2 responses have been considered regulatory. Interestingly, Th2 responses characterize a number of pulmonary diseases, many of which terminate in tissue remodeling and fibrosis. We developed a mouse model using Schistosoma mansoni eggs and cytokine-deficient mice to induce highly polarized Th1- or Th2-type inflammation in the lung. In this study, we examined the pathology and cytokine profiles in Th1- and Th2-polarized environments and used oligonucleotide microarray analysis to decipher the genes responsible for these effects. We further elaborated on the results using IL-10- and IL-13-deficient mice because these cytokines are believed to be the central regulators of Th2-associated pathology. We found that the Th1-polarized mice developed small granulomas with less fibrosis while expressing genes characteristic of tissue damage. Th2-polarized mice, in contrast, formed large granulomas with massive collagen deposition and up-regulated genes associated with wound healing, specifically, arginase, collagens, matrix metalloproteinases (MMPs), and tissue inhibitors of MMP. In addition, several members of the chitinase-like family were up-regulated in the lung following egg challenge. We also developed a method of defining the net collagen deposition using the expression profiles of several collagen, MMP, and tissue inhibitors of MMP genes. We found that Th1-polarized mice did not elaborate collagens or MMPs and therefore did not have a significant capacity for repair in this model. Thus, Th1-mediated inflammation is characterized by tissue damage, while Th2 directs wound healing and fibrosis.