Distinctive T Cell Patterns Defining Lymphocytic Alopecia and Alternate Autoimmune and Stem Cell Pathways, Linked to Pleiotropic Functions of Regulatory T Cells Within iSALT

Abstract:

The spectrum defining T-cell-mediated alopecias is an expression of autoimmune, innate, regenerative, and effete pathophysiological pathways. Four main folliculotropic T-cell patterns can be integrated into clinicopathologic aspects and define the majority of these alopecias. Lymphocytic inflammation targeting bulbs defines alopecia areata, and pan follicular lymphocytes sparing the hair bulbs and perifollicular concentric fibrosis define lichen planopilaris. Non-destructive lymphocytic folliculitis localized to the bulge modulating stem cell function is introduced as an unrecognized spectrum without defined alopecia. Pan follicular lymphocytic alopecia targets all levels of the follicle, including the bulb and sebaceous glands, and occurs in lupus erythematosus, follicular mucinosis, folliculotropic T-cell dyscrasia, and lymphoma. These form an evidence-based platform due to their inherent programmed pathways. Major advances have occurred in defining inducible mesenchymal skin associated with lymphoid tissue incorporating the pleiotropic functions of regulatory T cells integrated into the JAK/STAT activating transducer pathway. Beyond immunology, the integrated Tregs have non-immunologic functions that modulate stem cell pathways, regulate follicular cycles and follicular inflammation, and repair. In all T-cell alopecias, the central role of both CD8 ⁺ and Treg memory cells is pivotal in creating local, multifocal, and diffuse patterns of hair loss. The relationship between the stem cell niche localized to the bulge and supported by the stem cell niche forming progenitor bulbs that induce rapid transit amplifying basaloid cells and trichogenesis are explored in reference to both physiologic and pathogenic pathways. The expanding evidence-based studies defining the pleiotropic functions of the iSALT incorporated Treg/JAK/STAT pathways have led to the development of a conceptual framework to address T-cell alopecias.