Eosinophilia in transgenic mice expressing interleukin 5.

Abstract

Experiments in vitro suggest that although interleukin 5 (IL-5) stimulates the late stages of eosinophil differentiation, other cytokines are required for the generation of eosinophil progenitor cells. In this study transgenic mice constitutively expressing the IL-5 gene were established using a genomic fragment of the IL-5 gene coupled to the dominant control region from the gene encoding human CD2. Four independent eosinophilic transgenic lines have thus far been established, two of which with 8 and 49 transgene copies, are described in detail. These mice appeared macroscopically normal apart from splenomegaly. Eosinophils were at least 65- and 265-fold higher in blood from transgenics, relative to normal littermates, and approximately two- or sevenfold more numerous relative to blood from mice infected with the helminth Mesocestoides corti. Much more modest increases in blood neutrophil, lymphocyte, and monocyte numbers were noted in transgenics, relative to normal littermates (less than threefold). Thus IL-5 in vivo is relatively specific for the eosinophil lineage. Large numbers of eosinophils were present in spleen, bone marrow, and peritoneal exudate, and were highest in the line with the greatest transgene copy number. Eosinophilia was also noted in histological sections of transgenic lungs, Peyer's patches, mesenteric lymph nodes, and gut lamina propria but not in other tissues examined. IL-5 was detected in the sera of transgenics at levels comparable to those seen in sera from parasite-infected animals. IL-3 and granulocyte/macrophage colony-stimulating factor (GM-CSF) were not found. IL-5 mRNA was detected in transgenic thymus, Peyer's patches, and superficial lymph nodes, but not in heart, liver, brain, or skeletal muscle or in any tissues from nontransgenics. Bone marrow from transgenic mice was rich in IL-5-dependent eosinophil precursors. These data indicate that induction of the IL-5 gene is sufficient for production of eosinophilia, and that IL-5 can induce the full pathway of eosinophil differentiation. IL-5 may therefore not be restricted in action to the later stages of eosinophil differentiation, as suggested by earlier in vitro studies.

Inhibition of NFAT Specifically in T Cells Prevents Allergic Pulmonary Inflammation

“…IL-5 is a major growth factor for eosinophils and is important for eosinophil expansion in the lung during allergic airway disease (60,61). Overexpression of IL-5 in T cells or in the lung can promote lung eosinophilia (62,63). Since we did not observe decreased IL-5 levels in dnNFAT Tg mice and inhibition of NFAT did not affect IL-5 production by Th2 cells in vitro, this could explain why at late stages of allergic airway inflammation the accumulation of eosinophils in the lung is less affected.…”

IL‐33 activates eosinophils of visceral adipose tissue both directly and via innate lymphoid cells

“…AAMs in gonadal adipose tissue (GAT) are maintained by IL-4 and/or IL-13 [3]. The activation of eosinophils critically depends on IL-5: studies using il5-tg mice or il5-deficient mice and anti-IL-5 Ab have demonstrated that the expansion of eosinophils is largely regulated by IL-5 [4][5][6][7][8]. Il5-deficient mice show higher body weight and visceral adipose weight in response to a highfat diet [2].…”

Role of IL-5 in Innate and Adaptive Immunity to LarvalStrongyloides stercoralisin Mice

“…Depending on the transgenic construct, IL-5 overexpression has been shown to cause moderate (28) to massive eosinophilia, lower bowel inflammation, and enhanced autoantibody production (29,30). In the present study, two of these IL-5 transgenic mouse lines were utilized.…”