Differences between IL-4R alpha-deficient and IL-4-deficient mice reveal a role for IL-13 in the regulation of Th2 responses

Curr Biol. 1998 May 21;8(11):669-72. doi: 10.1016/s0960-9822(98)70256-8.


Allergens and infections with parasitic helminths preferentially induced Th2 immune responses associated with elevated levels of serum immunoglobulin E (IgE) and expansion of eosinophils and mast cells. Interleukin-4 (IL-4) is a key cytokine in the differentiation of naive CD4+ T cells into Th2 cells, which produce a panel of cytokines including IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13 [1] and have been shown to trigger recovery from gastrointestinal nematodes [2]. Nonetheless, mice deficient for IL-4 have been shown to develop residual Th2 responses [3-5] and can expel the nematode Nippostrongylus brasiliensis [6], suggesting that there is a functional equivalent of IL-4 in these processes. IL-13 is a cytokine that shares some, but not all, biological activities with IL-4 [7,8]. There is now compelling evidence that IL-4 and IL-13 share receptor components, including IL-4R alpha and IL-13R alpha 1 [9]. In order to dissect the roles of IL-4 and IL-13 in the regulation of Th2 cells and in the response to nematode infections, we looked for differences between mice deficient for either the IL-4 gene or the IL-4R alpha gene. Unlike IL-4, IL-4R alpha was required for control of N. brasiliensis, and Th2 development during infection--as characterized by cytokine production, GATA-3 and surface CD30 expression--was more severely affected in IL-4R alpha-/- mice than in IL-4-/- mice. Injection of recombinant IL-13 induced worm expulsion in otherwise incompetent RAG2-/- mice. Our results suggest that IL-13 regulates Th2 responses to nematode infection and requires IL-4R alpha.

Publication types

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

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism
  • Female
  • GATA3 Transcription Factor
  • Interleukin-13 / pharmacology
  • Interleukin-13 / physiology*
  • Interleukin-4 / deficiency*
  • Interleukin-4 / genetics
  • Interleukin-4 / physiology
  • Ki-1 Antigen / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Nippostrongylus
  • Receptors, Interleukin-4 / deficiency*
  • Receptors, Interleukin-4 / genetics
  • Receptors, Interleukin-4 / physiology
  • Recombinant Proteins / pharmacology
  • Strongylida Infections / genetics
  • Strongylida Infections / immunology
  • Strongylida Infections / therapy
  • Th2 Cells / immunology*
  • Trans-Activators / metabolism


  • DNA-Binding Proteins
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Interleukin-13
  • Ki-1 Antigen
  • Rag2 protein, mouse
  • Receptors, Interleukin-4
  • Recombinant Proteins
  • Trans-Activators
  • V(D)J recombination activating protein 2
  • Interleukin-4