Th1 and Th2 cells are required for both eosinophil- and neutrophil-associated airway inflammatory responses in mice

Abstract

Most current animal models focus on eosinophil-mediated asthma, despite compelling evidence that a neutrophil-mediated disease occurs in some asthma patients. Using intranasal challenge of mice sensitized either orally or nasally with whole peanut protein extract in the presence of cholera toxin, we developed mouse models of eosinophil-and neutrophil-mediated asthma, respectively. In this study, mice deficient in Th1 (IL-12 and IFN-γ) or Th2 (IL-4 and IL-13) pathways were used to characterized the role played by Th1 and Th2 cytokines during the initial priming phase in the two models.. Antigen-specific Ab responses were controlled primarily by Th2 cytokines in mice sensitized by the oral route, whereas Th1 cytokines appeared to play a predominant role in mice sensitized by the nasal route. Furthermore, the absence of key Th1 or Th2 cytokines during the initial phase of priming reduced lung reactivity in both mouse models of airway inflammation.

Inflammatory Role of ASC in Antigen-Induced Arthritis Is Independent of Caspase-1, NALP-3, and IPAF

“…In this context, we were most surprised to observe that Ag-specific IgG levels (total, IgG1 and IgG2a) were not affected in ASC Ϫ/Ϫ mice as predicted during a Th1 to Th2 shift (49,50). We currently have no explanation for this discrepancy, but such discrepancy has already been observed in other experimental situations (51)(52)(53)(54).…”

Eosinophil-derived IFN-γ induces airway hyperresponsiveness and lung inflammation in the absence of lymphocytes

“…[25][26][27][28][29] However, few studies in human subjects and mice have reported on the positive contribution of T H 1 lymphocytes and IFN-g to allergic lung inflammation. [30][31][32][33] These discrepancies might be in part attributed, as pointed out by some of these authors, to differences in experimental models (dose, timing, and means of IFN-g or anti-IFN-g administration; use of IFN-g-or IFN-g receptor-deficient animals and genetic background) but might also reflect a dual role for IFN-g, as recently suggested for autoimmune diseases. 34 Nevertheless, the positive or negative effects observed on airway inflammation were considered to target or arise from lymphocytes.…”

A common intronic variant of CXCR3 is functionally associated with gene expression levels and the polymorphic immune cell responses to stimuli

“…By using knockout model mice for IFNG or IL4 and/or IL13 genes, it was also shown that both T H 1 and T H 2 cells were required for both eosinophiland neutrophil-associated airway inflammation. 25 Evidence for CXCR3's functions in atopic responses of asthma has also been found. Thomas et al 26 suggested that CXCR3 plays a role in inflammatory T-cell recruitment to the bronchoalveoli during the allergic inflammatory response by using an endobronchial segmental allergen challenge in human atopic asthmatic subjects.…”