transforming-growth-factor-beta and Lichen-Planus

Skin protects body from continual attack by microbial pathogens and environmental factors. Such barrier function of skin is achieved by multiple components including immune system, which is mainly regulated by lymphocytes. T lymphocytes (T cells) that express T cell receptor (TCR) α and β chains (αβT cells) control the strength and the type of immune response. CD4T cell population consists of helper T (Th) cell-subsets and immunosuppressive regulatory T (Treg) cells. Th1 cells produce IFN-γ and protect against intracellular pathogens. Th2 cells produce IL-4 family cytokines and participate in allergic skin diseases, including atopic dermatitis (AD). Th17 cells secrete IL-17, recruit granulocytes to fight against extracellular microorganisms, and play a role in psoriasis and AD. Th22 cells produce IL-22 that activates epithelial cells and mediates acanthosis in psoriasis and AD. On the other hand, Foxp3+ Treg cells attenuate immune responses partly via TGF-β or IL-10. Tissue resident memory T (Trm) cells in the skin-most of which are epidermal CD8T cells-constitute the first line of the defense against repeated infections. CD8 T cells are also engaged in psoriasis, lichen planus, and drug eruptions. Skin harbors innate-like αβT cells such as natural killer T (NKT) cells as well, whose function is not fully revealed. Understanding these αβT cells helps to comprehend skin diseases.

Topics: Animals; CD8-Positive T-Lymphocytes; Cell Differentiation; Cell Membrane; Cytokines; Dermatitis, Atopic; Drug Eruptions; Forkhead Transcription Factors; Humans; Hypersensitivity; Interleukin-10; Interleukin-17; Keratinocytes; Killer Cells, Natural; Lichen Planus; Mice; Phenotype; Skin; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; Th1 Cells; Th2 Cells; Transforming Growth Factor beta

Transforming growth factor-beta1 (TGF-β1) is expressed in normal epidermis. TGF-β1 potently inhibits keratinocyte proliferation and immunomodulatory properties, mainly by suppressing immune responses to self-antigens. Lichen planus (LP) is a form of dermatitis caused by cell-mediated immune dysfunction, but the exact pathogenic pathways are unknown, which poses therapeutic challenges. We report on a 68-year-old man who developed multiple pruritic, discrete, and well-demarcated, flat-topped red-purple papules and macules on the back and upper arms following 4 cycles of treatment with TGF-β receptor I (TGFBR-I) inhibitor, ly3200882, for metastatic chondrosarcoma. The biopsy showed hyperkeratosis, wedge-shaped hypergranulosis, elongation of the rete ridges, and a dense band-like lymphohistiocytic infiltrate admixed with colloid bodies and pigment incontinence, consistent with LP. Temporal correlation suggested that the TGFBR-I inhibitor might be a trigger. Treatment with topical clobetasol and oral metronidazole led to partial resolution of the lesions with postinflammatory hyperpigmentation. We believe this is the first reported case of LP related to TGFBR-I inhibitor therapy. This report expands the list of cutaneous adverse events associated with this novel class of targeted therapy. More importantly, this report supports emerging evidence that failure of TGF-β1 activation/signal transduction is an important mechanism in the pathogenesis of LP and suggests the TGF-β1 pathway as a potential therapeutic target in this disease.

Topics: Administration, Oral; Administration, Topical; Aged; Anti-Bacterial Agents; Anti-Inflammatory Agents; Chondrosarcoma; Clobetasol; Drug Therapy, Combination; Humans; Hyperpigmentation; Lichen Planus; Male; Metronidazole; Transforming Growth Factor beta; Treatment Outcome

Folliculitis decalvans (FD) is a rare variant of primary cicatricial alopecia, for which the etiopathogenesis remains unclear. Our purpose was to evaluate whether certain immunologic mechanisms might have a significant role in the pathogenesis of FD. Lesional scalp biopsy specimens from 7 patients with FD, 7 with lichen planopilaris, and 4 with alopecia areata were studied immunohistochemically by using monoclonal antibodies to CD1a, CD3, CD4, CD8, CD20, CD25, HLA-DR, interleukin (IL)-1beta, IL-4, IL-8, interferon gamma, tumor necrosis factor alpha, basic fibroblast growth factor (b-FGF), transforming growth factor (TGF)-beta, endothelial leukocyte adhesion molecule 1, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule. We showed that early FD lesions are characterized by an infiltration of activated T-helper cells, featuring mixed TH1/TH2 polarization. IL-8 and ICAM-1 may contribute to the infiltration of neutrophils, whereas b-FGF and TGF-beta may represent important mediators of the fibrosis that characterizes late-phase FD.

Topics: Adult; Aged; Alopecia; Alopecia Areata; Female; Fibroblast Growth Factor 2; Humans; Immunohistochemistry; Intercellular Adhesion Molecule-1; Interleukin-8; Lichen Planus; Male; Middle Aged; T-Lymphocytes; Transforming Growth Factor beta

To evaluate the expression of fibrogenic cytokines in lichen sclerosus (LS) infiltrate as compared with lichen planus (LP) infiltrate.. Eight cases of vulvar LS (early stage, n = 3; well developed or old, n = 5) and 4 of vulvar LP were studied. Monoclonal antibodies directed against some of the major fibrogenic cytokines (IL-4, TGF-beta, IL-6) and against IFN-gamma, which inhibits collagen synthesis, were used per the alkaline phosphatase/anti-alkaline phosphatase technique on frozen sections.. Staining for IL-4 revealed higher expression of fibrogenic cytokines (more than 50% infiltrating cells) in the LS infiltrate, mainly in early lesions, than in LP. Conversely, staining for IFN-gamma in LS was poor (less than 10% infiltrating cells), while strong positivity (more than 60% infiltrating cells) was found in LP. Staining for TGF-beta, a mediator of fibrosis in scleroderma, was similar in both LS and LP dermis.. This study showed the immunohistochemical expression of fibrogenic cytokines in vulvar LS, with a different pattern as compared to that of LP. It is conceivable that dermal infiltrating cells actively participate, via cytokine production, in the pathogenesis of fibrosis in LS.

Topics: Adult; Aged; Cytokines; Epidermis; Female; Humans; Immunohistochemistry; Interferon-gamma; Interleukin-4; Interleukin-6; Lichen Planus; Lichen Sclerosus et Atrophicus; Middle Aged; Skin; Transforming Growth Factor beta; Vulvar Diseases