Figure 2-. Participation of Type 2 and Type 3 Lymphocytes in Cutaneous Tissue Repair.

Left: The type 2 immune response to skin injury is triggered by release of alarmins such as TSLP, IL-18, and IL-33 from damaged keratinocytes, endothelial cells, and stromal cells. Locally resident type 2 lymphocytes such as ILC2s sense these tissue damage signals and produce IL-4, IL-13, and amphiregulin in response. These cytokines promote wound closure by activating wound-contracting myofibroblasts, both directly by signaling to nearby fibroblasts and indirectly by inducing alternative activation of macrophages (AAM). Type 2 cytokines are also capable of driving keratinocyte proliferation and therefore may promote re-epithelialization.

Right: Type 3 lymphocytes are abundant in skin and respond to both microbial ligands and tissue damage signals released by keratinocytes and myeloid cells, including IL-1β and IL-23. IL-17 and IL-22 produced by these cells act directly on keratinocytes, resulting in a two-pronged tissue protective response. First, antimicrobial immunity is bolstered by neutrophil recruitment and antimicrobial peptide production. Secondly, these cytokines reinforce the epidermal barrier by driving keratinocyte proliferation to cover injury sites at the expense of keratinocyte maturation.

Solid arrows, known interactions; Dotted arrows, likely interactions based on data from other tissues and contexts.