Unique protein signatures evolve during the course of a delayed‐type hypersensitivity reaction in human skin

Han, Joseph; Stratman, Scott; Young, Jade N; Poplausky, Dina; Owji, Shayan; Luu, Yen; Estrada, Yeriel; Rosa, Joel Correa da; Krueger, James G.; Gulati, Nicholas

doi:10.1111/1346-8138.16688

Cited by 2 publications

(1 citation statement)

References 14 publications

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“…38,39 Furthermore, microbiota-specific memory CD4 + CD25 + ICOS + effector T cells have been described in the intestinal tissue of patients with inflammatory bowel disease. 40 PD-1 is increased in skin following DPCP challenge as measured in a protein array 41 which corroborates the expression of PD-1 on many subsets including CD4 + CD25 + ICOS + and all CD8 + TRM clusters identified by unsupervised analysis of flow cytometry data.…”

Section: Discussionsupporting

confidence: 71%

Oral prednisone regulates human skin T cells in delayed‐type hypersensitivity reaction elicited by diphencyprone

Mehta

Jack

Maari

et al. 2023

Allergy

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Background The potential benefit of inducing delayed‐type hypersensitivity (DTH) reaction in healthy volunteers (HVs) as experimental models to study skin inflammatory disorders was recently reported using bulk molecular technologies. Immunophenotype of skin T cells, including cellular source of Type 1, 2, and 3 cytokines, in a local DTH reaction and their modulation by oral drugs remain to be investigated. Method Purified protein derivative (PPD), nickel, diphencyprone (DPCP), or house dust mite (HDM) was administered as sensitizer to 40 HVs. In addition, 20 HVs were randomized to receive oral prednisone or placebo before DPCP challenge. We characterized the immunophenotype and cytokine profile of CD3+ T cell infiltrate, and examined the modulation by oral prednisone at single‐cell level using multiparameter flow cytometry and unsupervised analysis. Results PPD was biased toward a Th1 and Tc1 response, and HDM a Th2/Th17 and Tc2. Nickel and DPCP displayed a mixed Th1/Th2/Th17 and Tc1 response. CD4+CD25+FoxP3+ regulatory T cells (Tregs), the minor CD4+CD25+FoxP3−ICOS+PD‐1+ (activated PD‐1+ Th), and CD103+ tissue resident memory (TRM) cells were detected in all groups. DPCP uniquely elicited rare CD8+CD103+CD25+RoRγt+PD‐1+ICOS+IFNγ+ T cells (activated CD8+IFNγ+PD‐1+ TRM). Oral prednisone decreased frequencies of activated PD‐1+ Th and CD8+IFNγ+PD‐1+ TRM subsets relative to placebo in DPCP reaction. The latter was positively correlated with improvement of clinical parameters with prednisone. Conclusion DTH and skin CD3+ T cell profiles elicited by common sensitizers can be modulated by oral drugs. Corticosteroids reduce the frequencies of activated PD‐1+ Th and CD8+IFNγ+PD‐1+ TRM cells after DPCP exposure.

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