Hidradenitis Suppurativa Is Characterized by Dysregulation of the Th17:Treg Cell Axis, Which Is Corrected by Anti-TNF Therapy

Abstract

Hidradenitis suppurativa (HS) is a chronic, inflammatory, and debilitating disease of hair follicles with 1-4% prevalence and high morbidity. There is a dearth of information on the pathogenesis and immune dysregulation underlying HS; therefore, we carried out a detailed analysis of skin-infiltrating T cells. Cells isolated from skin biopsy samples and blood from HS patients and healthy control subjects were analyzed by 16-parameter flow cytometry to provide detailed profiles of CD4 T-cell subsets. We observed substantial infiltration of inflammatory T cells with a striking T helper (Th) type 17-skewed cytokine profile in HS skin; these cells expressed the Th17 lineage marker CD161 and IL-17, as well as proinflammatory cytokines GM-CSF, IL-22, IFN-γ, and tumor necrosis factor. Regulatory T cells were also enriched in HS lesional skin; however, the ratio of Th17 to regulatory T cells was nonetheless highly dysregulated in favor of Th17 cells. In contrast, lesional skin from anti-tumor necrosis factor-treated HS patients who showed substantial clinical improvement exhibited a significant reduction in the frequency of Th17 cells and normalization of the Th17 to regulatory T cell ratio. These data suggest that inhibition of pathogenic IL-17 via tumor necrosis factor blockade is associated with improvement in immune dysregulation in HS and may provide a rationale for targeting IL-17 in the disease.

Frequency of circulating subpopulations of T‐regulatory cells in patients with hidradenitis suppurativa

“…However, to the best of our knowledge only one previous study investigated the number of Tregs (CD4+ CD127 low FoxP3+) in blood samples of HS patients and found no difference between HS patients compared to healthy controls. Of note, in contrast to our study, they included a smaller number of patients and CD25 was not used as an additional Tregs marker . Analysis of skin biopsies, however, demonstrated a significant increased number of CD4+ FoxP3+ CD127 low Tregs within lesional HS skin compared with healthy controls …”

“…Of note, in contrast to our study, they included a smaller number of patients and CD25 was not used as an additional Tregs marker . Analysis of skin biopsies, however, demonstrated a significant increased number of CD4+ FoxP3+ CD127 low Tregs within lesional HS skin compared with healthy controls …”

“…This homeostasis can be hampered by an altered bacterial biofilm on the skin, as demonstrated by the analysis of punch biopsies from clinically unaffected HS skin . In addition, in lesional skin of HS patients available data showed a significant increased ratio of Th17:Tregs compared to healthy controls, suggesting a possible imbalance in favour of inflammatory effector T‐cell subsets . Similarly, studies in skin of patients with psoriasis reported an increased Th17:Tregs ratio with a positive correlation with disease severity .…”

Elevated levels of the antimicrobial peptide LL‐37 in hidradenitis suppurativa are associated with a Th1/Th17 immune response

“…To this end, we investigated the expression of LL‐37 and CAMP in HS, PS, AD and healthy skin by immunohistochemistry and semi‐quantitative real‐time PCR and compared whether LL‐37 peptide and CAMP mRNA levels correlate with lesional HS skin. In addition, we examined what kind of cells (T cells, macrophages and neutrophils) and cytokines (IFN‐γ, IL‐17, IL‐23, IL‐32, IL‐1β, TNF‐α and IL‐10), which are known to be elevated in HS correlate with the presence of LL‐37. To complete our analysis, we investigated the impact of LL‐37 on the proliferation of lectin‐stimulated CD4 + and CD8 + T cells isolated from the blood of healthy donors and patients with HS and delineated by calcium assay, how LL‐37 impacts proliferation of T cells directly.…”

The Magnitude of mTORC1 Signalling May Predict the Response to Isotretinoin Treatment in Patients with Hidradenitis Suppurativa

“…Notably, the differentiation of Th17 cells is controlled by mTORC1, which promotes Th17 differentiation [8,9]. Moran et al [10] recently confirmed substantial infiltration of inflammatory Th17 cells with a striking Th17-skewed cytokine profile in HS skin. Upregulation of mTORC1 has been observed in common inflammatory IL-17-driven dermatoses such as psoriasis, acne…”