The Role of Pro-Healing T-Cells in Wound Responses in an Atopic Environment

The atopic environment diminished the pro-healing T-cell populations, attenuating wound healing responses, a study found. These study findings were published in The Journal of Investigative Dermatology.

This study evaluated atopic dermatitis (AD)-like symptoms using Stat6VT mice. Differences in ear tissue features from AD-like mice and controls were compared using flow cytometry and immunofluorescence.

Dendritic epidermal T-cell (DETC) populations have been linked with wound healing. In order to evaluate when in development DETCs may be lost in AD, T-cell numbers in the skin were evaluated from birth. By day 10, Stat6VT mice had lower DETC numbers in their skin than controls.

Despite this observation, the Stat6VT mice exhibited similar numbers of CD4⁺ and CD8⁺ T-cells and DETC activation markers as controls, signifying they were phenotypically comparable with controls. Stat6VT mice had DETCs which were more prone to death than wild type cells, indicating fewer viable cells post-activation (P <.001).

As Stat6VT mice develop a Th2-dominant environment and the Th2 cytokine, interleukin (IL)-4, is known to affect DETC homeostasis, the investigators examined the role of IL-4 in DETC regulation. Control and Stat6VT mice were found to have similar IL-4 receptor expression in DETCs. Crossing Stat6VT mice with IL-4-deficient mice restored the level of DETCs comparable with controls (P <.05).

To investigate if IL-4 could reduce DETC numbers in wild-type mice, controls were injected with exogenous IL-4. This treatment decreased the frequency of DETCs comparable with Stat6VT mice (P >.05).

Next, an IL-4 blockage was evaluated in Stat6VT mice to assess whether DETC numbers could be rescued. An anti-IL-4 treatment every other day for a week did not restore DETC levels.

To evaluate how these observations contributed to wound healing, an ear skin wounding assay was conducted. After injury, the numbers of DETCs in controls expanded dramatically (P <.001) but not in Stat6VT mice (P >.05). At 3 days post-injury, Stat6VT ears were thicker than controls (P <.001) and had impaired wound closure (P <.01).

A fibroblast growth factor seven (FGF7) supplement was evaluated in this wound healing model as FGF7 is produced by DETCs. Intradermal FGF7 treatment diminished Stat6VT tissue swelling comparable with controls with reduced ear thickness and improved wound closure.

The researchers believe that their study data demonstrated that in an atopic-like environment, IL-4 promoted the elimination of DETC from skin tissue which resulted in diminished wound healing. Replacing pro-healing cytokines with an FGF7 treatment was observed to recover the rate of healing, which suggested to them that a similar therapy may be beneficial for patients with AD.

Reference

Wang J, Pajulas A, Fu Y, et al. γδ T cell-mediated Wound Healing is Diminished by Allergic Skin Inflammation.J Invest Dermatol. 2022;S0022-202X(22)00255-X. doi:10.1016/j.jid.2022.03.012