Cross‐sectional associations between cutaneous viral infections and regulatory T lymphocytes in circulation

Abstract

Summary Background Cutaneous viral infections and immune suppression are risk factors for some forms of nonmelanoma skin cancer; however, their interrelationship is poorly understood. Objectives To examine cross‐sectional associations between cutaneous viral infections and circulating forkhead‐box P3 (FOXP3)‐expressing T‐regulatory (Treg) cells, suppressive cells that dampen effective antitumour immunity. Materials and methods Blood, eyebrow hair (EBH) and skin swab (SSW) samples were collected from 352 patients 60 years and older undergoing skin screening, without prevalent skin cancer, while participating in an ongoing prospective cohort study of cutaneous viral infections and skin cancer. DNA corresponding to 98 cutaneous human papillomavirus (HPV) types and five human polyomaviruses (HPyV) was assessed in EBH and SSW. Distinct classes of circulating Treg‐cell subpopulations were defined by flow cytometry including cutaneous lymphocyte antigen (CLA) and CCR4high Treg cells, both previously associated with cutaneous diseases. Age‐ and sex‐adjusted associations between circulating T‐cell populations and infection were estimated using logistic regression. Results Total Treg‐cell proportion in peripheral blood was not associated with β HPV or HPyV infection. However, the proportion of circulating CLA+ Treg cells was inversely associated with γ HPV EBH infection [odds ratio (OR) 0·54, 95% confidence interval (CI) 0·35–0·84]. Interestingly, circulating Treg cells expressing markers indicative of antigen activation (CD27–CD45RA–FOXP3+CD4+) were also inversely associated with γ HPV infection in SSW (OR 0·55, 95% CI 0·30–0·99) and EBH (OR 0·56, 95% CI 0·36–0·86). Conclusions Inverse associations between circulating Treg cells and γ HPV infection suggest that localized viral infection may promote immunosuppressive cell migration into skin.

Cutaneous viral infections associated with ultraviolet radiation exposure

“…The VIRUSCAN Study is a prospective cohort study of cutaneous viral infections, UVR exposure and KC development among skin cancer screening patients in Tampa, FL 16 . The study design and population have been described in detail previously 16,36,37 . Briefly, study participants were individuals, ages 60+ years, undergoing routine skin cancer screening exams at the University of South Florida Dermatology Clinic.…”

“…Patients were eligible with a history of either BCC or SCC, but were excluded if they had both BCC and SCC. At the enrollment visit, participants underwent a routine total body skin examination during which suspicious skin lesions were biopsied; they also completed a questionnaire and contributed blood, EBH and forearm SSW samples for the measurement of cutaneous viral infection biomarkers 16,36,37 . A spectrophotometer was used to measure the degree of pigmentation of sun‐exposed skin relative to sun‐unexposed skin as an indicator of recent UVR exposure 35 …”

“…16 The study design and population have been described in detail previously. 16,36,37 Briefly, study participants were individuals, ages 60+ years, undergoing routine skin cancer screening exams at the University of South Florida Dermatology Clinic. Patients were eligible with a history of either BCC or SCC, but were excluded if they had both BCC and SCC.…”

“…At the enrollment visit, participants underwent a routine total body skin examination during which suspicious skin lesions were biopsied; they also completed a questionnaire and contributed blood, EBH and forearm SSW samples for the measurement of cutaneous viral infection biomarkers. 16,36,37 A spectrophotometer was used to measure the degree of pigmentation of sun-exposed skin relative to sun-unexposed skin as an indicator of recent UVR exposure. 35 A total of 1303 skin cancer screening patients were enrolled in the VIRUSCAN Study between July 15, 2014 and August 31, 2017, of whom 124 were diagnosed with KC as a result of the initial screening exam and were excluded.…”

Are regulatory T cells associated with cutaneous viral infections?

“…In this issue of the BJD , Hampras et al . investigate the association between cutaneous viruses and circulating Treg cells . The authors correlated the frequency of circulating Treg cells with the presence of beta and gamma HPV and human polyomavirus (HPyV) DNA in eyebrow hair and skin from 352 patients attending a skin cancer screening clinic as part of an ongoing study on cutaneous viral infections and skin cancer.…”