Reorganization and functional divergence of the CD4+ memory T cell compartment in hidradenitis suppurativa

Abstract

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with poorly understood and complex pathophysiology with interplay between many immune and stromal cells. While the T cell infiltrate in HS is well-documented, the relationship between systemic memory T cells and those within the cutaneous microenvironment has yet to be fully elucidated. We performed a comparative analysis of skin and peripheral blood mononuclear cells (PBMCs) samples from HS patients and healthy controls using flow cytometry to evaluate T cell subsets and their cytokine profile with focus on TNF-α, IFN-γ, IL-17A. Within the memory compartment, CD4+ central memory T cells (TCM) were profoundly expanded in HS lesions (21%) compared to healthy skin (<1%). A positive correlation was observed between the levels of skin-infiltrating TCM and those found in the systemic circulation. Conversely, CD4+ resident memory T cells (TRM) were significantly depleted in HS lesions (~30% to <10%). Functional assays revealed a marked discordance between tissues; skin-derived memory cells exhibited a hyper-responsive phenotype, producing significantly higher levels of TNF-α, IFN-γ, and IL-17A than matched PBMCs. These data suggest that HS is characterized by a synchronized peripheral-lesional axis of CD4+ TCM cells. The TRM deficit may reflect phenotypic plasticity or retrograde migration during chronic inflammation. Crucially, the HS microenvironment appears to reprogram recruited memory cells, leading to a tissue-specific functional activation not reflected in the systemic circulation.