The Primary Binding Subunit of the Human Interleukin-4 Receptor Is Also a Component of the Interleukin-13 Receptor

Abstract

Interleukin (IL)-13 elicits a subset of the biological activities of the related IL-4. The basis of this functional similarity is that their specific cell-surface receptors (called IL-13R and IL-4R) are distinct, yet are complex and share a common subunit(s). The IL-4R primary binding subunit (called IL-4R alpha) does not by itself bind IL-13. We show that the ability of IL-13 to partially compete for IL-4 binding to some human cell types depended on co-expression of IL-4R and IL-13R. However, IL-13 binding was always associated with IL-4 binding. Hyper-expression of IL-4R alpha on cells expressing both IL-4R and IL-13R decreased their binding affinity for IL-4, abrogated the ability of IL-13 to compete for IL-4 binding, and yet had no effect on IL-13R properties. Anti-human IL-4R alpha monoclonal antibodies which blocked the biological function and binding of IL-4 also blocked the function and binding of IL-13. These data show that IL-4R alpha is a secondary component of IL-13R.

Immunity to gastrointestinal nematode infections

“…66 Furthermore, with the exception of IL-4 in the skin, 67 IL-4 appears to be dispensable for N. brasiliensis expulsion. 61,68 The redundancy between IL-4 and IL-13 likely stems from their shared usage of the IL-4Ra subunit, [69][70][71] although interestingly, IL-4Ra deficiency in T cells has no impact on worm expulsion during either T. spiralis, 72 H. polygyrus, 73 or N. brasiliensis 61,62 infections, in contrast to total IL-4Ra ablation. 63,[73][74][75] Instead, IL-4 might need to be produced rather than recognized by T cells, as it is mostly secreted by follicular helper T cells to promote IgG1 class switching of B cells.…”

The biology of Stat4 and Stat6

“…The overlapping functional and biochemical activities of IL-4 and IL-13 can be explained by the fact that their receptors share the IL-4Ra chain (Lin et al, 1995;Zurawski et al, 1995). Unlike IL-4, the IL-4Ra chain is unable to recognize IL-13 by itself, but when combined with the IL-13Ra chain the complex binds IL-13 with a high a nity (Aman et al, 1996;Hilton et al, 1996).…”

Th1/Th2 cytokine balance in arthritis

“…However, the effect of IL-4 on T cells appears more potent than that of IL-13. Furthermore, the 2 cytokines use the same multichain receptor, but in a competitive manner, as shown particularly with activated synoviocytes (23). The reason for the presence of the 2 molecules is unclear, and the use of one or the other cytokine for treatment would be difficult to justify.…”