IL-4 and IL-13: Regulators and Effectors of Wound Repair

Annu Rev Immunol. 2023 Apr 26:41:229-254. doi: 10.1146/annurev-immunol-101921-041206. Epub 2023 Feb 3.

Abstract

Type 2 immunity mediates protective responses to helminths and pathological responses to allergens, but it also has broad roles in the maintenance of tissue integrity, including wound repair. Type 2 cytokines are known to promote fibrosis, an overzealous repair response, but their contribution to healthy wound repair is less well understood. This review discusses the evidence that the canonical type 2 cytokines, IL-4 and IL-13, are integral to the tissue repair process through two main pathways. First, essential for the progression of effective tissue repair, IL-4 and IL-13 suppress the initial inflammatory response to injury. Second, these cytokines regulate how the extracellular matrix is modified, broken down, and rebuilt for effective repair. IL-4 and/or IL-13 amplifies multiple aspects of the tissue repair response, but many of these pathways are highly redundant and can be induced by other signals. Therefore, the exact contribution of IL-4Rα signaling remains difficult to unravel.

Keywords: extracellular matrix; helminths; inflammation; tissue injury; type 2 immunity.

Publication types

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

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Fibrosis
  • Helminths
  • Humans
  • Interleukin-13*
  • Interleukin-4*

Substances

  • Cytokines
  • Interleukin-13
  • Interleukin-4