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The Contributory Roles of Th17 Lymphocyte and Cytotoxic T Lymphocyte at the Hair Bulge Region as Well as the Hair Bulb Area in the Chronic Alopecia Areata Patients

View Article: PubMed Central - PubMed

ABSTRACT

Background: Alopecia areata (AA) is a T cell-mediated autoimmune disease that targets hair follicles and interrupts hair regrowth. The microenvironment of the effector T cells and their related cytokines may affect immunopathogenesis around the hair bulb/bulge.

Objective: To determine the contributory roles of the effector T cell subsets and related cytokines to the pathogenesis of AA.

Methods: We investigated the correlation between histopathological grades and four clinical prognostic factors in 331 patients with AA, and analyzed the topography of T cell infiltrates and related cytokines around the hair bulb/bulge according to histopathological grades through immunohistochemical and double immunofluorescence studies on a subset of AA specimens.

Results: First, the groups with more severe histopathological grades were associated with earlier onset, longer duration, more hair loss, as well as poorer therapeutic outcomes. Second, the pattern of CD4 and CD8 expression around the hair bulb/bulge varied by histopathological grade, with staining density decreasing in the following order: type 1>type 2>type 3. In addition, interferon-γ and transforming growth factor-β1 expression appeared denser in the peribulbar area. Interestingly, the denser CCR6+ cells (Th17 cells) showed more infiltration than CCR5+ cells (Th1 cells) around the hair bulb/bulge as histopathological grade worsened.

Conclusion: The insidious destruction of bulge stem cells and hair bulb matrix stem cells results in more severe hair loss in patients with chronic AA, which is mediated by Th17 lymphocyte and cytotoxic T lymphocyte infiltration. Furthermore, Th17 lymphocytes may play an even more important role than cytotoxic T cells in the development of AA.

No MeSH data available.


Related in: MedlinePlus

Immunnohistochemistry for transforming growth factor (TGF)-β1. Expression of TGF-β1 was detected in the outer root sheath keratinocyte, regressing epithelial strand, dermal sheath and dermal sheath cells, and its expression was correlated with histopathologic grading (A~C, ×100; D~F, ×200).
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Figure 7: Immunnohistochemistry for transforming growth factor (TGF)-β1. Expression of TGF-β1 was detected in the outer root sheath keratinocyte, regressing epithelial strand, dermal sheath and dermal sheath cells, and its expression was correlated with histopathologic grading (A~C, ×100; D~F, ×200).

Mentions: IFN-γ+ cells infiltrated the dermis around the hair bulb and the more severe disease groups by histopathological grade showed denser expression of IFN-γ (Fig. 6). TGF-β1 was expressed in the epithelia of the outer root sheath, regressive epithelial strand, fibrous dermal sheath, and dermal sheath cells induced by inflammatory changes. The more severe disease group by histopathological grade also showed denser expression of TGFβ-1 (Fig. 7). Interestingly, TGF-β2 was expressed primarily in the dermal papilla area, and the more severe disease group by histopathological grade showed less expression of TGF-β2 as the size of the dermal papilla area decreased (Fig. 8).


The Contributory Roles of Th17 Lymphocyte and Cytotoxic T Lymphocyte at the Hair Bulge Region as Well as the Hair Bulb Area in the Chronic Alopecia Areata Patients
Immunnohistochemistry for transforming growth factor (TGF)-β1. Expression of TGF-β1 was detected in the outer root sheath keratinocyte, regressing epithelial strand, dermal sheath and dermal sheath cells, and its expression was correlated with histopathologic grading (A~C, ×100; D~F, ×200).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5383740&req=5

Figure 7: Immunnohistochemistry for transforming growth factor (TGF)-β1. Expression of TGF-β1 was detected in the outer root sheath keratinocyte, regressing epithelial strand, dermal sheath and dermal sheath cells, and its expression was correlated with histopathologic grading (A~C, ×100; D~F, ×200).
Mentions: IFN-γ+ cells infiltrated the dermis around the hair bulb and the more severe disease groups by histopathological grade showed denser expression of IFN-γ (Fig. 6). TGF-β1 was expressed in the epithelia of the outer root sheath, regressive epithelial strand, fibrous dermal sheath, and dermal sheath cells induced by inflammatory changes. The more severe disease group by histopathological grade also showed denser expression of TGFβ-1 (Fig. 7). Interestingly, TGF-β2 was expressed primarily in the dermal papilla area, and the more severe disease group by histopathological grade showed less expression of TGF-β2 as the size of the dermal papilla area decreased (Fig. 8).

View Article: PubMed Central - PubMed

ABSTRACT

Background: Alopecia areata (AA) is a T cell-mediated autoimmune disease that targets hair follicles and interrupts hair regrowth. The microenvironment of the effector T cells and their related cytokines may affect immunopathogenesis around the hair bulb/bulge.

Objective: To determine the contributory roles of the effector T cell subsets and related cytokines to the pathogenesis of AA.

Methods: We investigated the correlation between histopathological grades and four clinical prognostic factors in 331 patients with AA, and analyzed the topography of T cell infiltrates and related cytokines around the hair bulb/bulge according to histopathological grades through immunohistochemical and double immunofluorescence studies on a subset of AA specimens.

Results: First, the groups with more severe histopathological grades were associated with earlier onset, longer duration, more hair loss, as well as poorer therapeutic outcomes. Second, the pattern of CD4 and CD8 expression around the hair bulb/bulge varied by histopathological grade, with staining density decreasing in the following order: type 1>type 2>type 3. In addition, interferon-γ and transforming growth factor-β1 expression appeared denser in the peribulbar area. Interestingly, the denser CCR6+ cells (Th17 cells) showed more infiltration than CCR5+ cells (Th1 cells) around the hair bulb/bulge as histopathological grade worsened.

Conclusion: The insidious destruction of bulge stem cells and hair bulb matrix stem cells results in more severe hair loss in patients with chronic AA, which is mediated by Th17 lymphocyte and cytotoxic T lymphocyte infiltration. Furthermore, Th17 lymphocytes may play an even more important role than cytotoxic T cells in the development of AA.

No MeSH data available.


Related in: MedlinePlus