Role of T helper 17 cells and T regulatory cells in alopecia areata: comparison of lesion and serum cytokine between controls and patients

Loh, Seung-Hee; Moon, Haena; Lew, Bark‐Lynn; Sim, Woo‐Young

doi:10.1111/jdv.14775

Cited by 62 publications

(74 citation statements)

References 20 publications

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“…Studying scalp biopsies and serum samples from AA patients, they found out that lesional IL‐17, IL‐22, and serum IL‐1, IL‐17, TNF‐α, and TGF‐β were significantly higher in AA patients than in controls. Moreover, they demonstrated that there were positive correlations between lesional and serum IL‐17 and disease severity …”

Section: Il‐17 and Autoimmune Skin Diseasesmentioning

confidence: 99%

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IL‐17 and its role in inflammatory, autoimmune, and oncological skin diseases: state of art

et al. 2019

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Recent data support the theory of the involvement of IL‐17 in the pathogenesis of several chronic inflammatory skin diseases (psoriasis, atopic dermatitis, acne, hidradenitis suppurativa) and autoimmune skin diseases (alopecia areata, vitiligo, bullous diseases). Even if the role of IL‐17 in inflammatory and autoimmune diseases has been reported extensively, its role in tumor is still controversial. Some reports show that Th17 cells eradicate tumors, while others reveal that they promote the initiation and early growth of tumors. Herein, we review the role of IL‐17 in the involvement of some common dermatologic diseases: psoriasis, atopic dermatitis, hidradenitis suppurativa, acne, vitiligo, melanoma, and nonmelanoma skin cancers.

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Section: Il‐17 and Autoimmune Skin Diseasesmentioning

confidence: 99%

“…Recent evidences highlighted the role of both Th17 cells and T regulatory (Treg) cells in the pathogenesis of alopecia areata (AA) . Loh et al .…”

Section: Il‐17 and Autoimmune Skin Diseasesmentioning

confidence: 99%

IL‐17 and its role in inflammatory, autoimmune, and oncological skin diseases: state of art

et al. 2019

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“…Depression and anxiety experienced by patients with AA were measured using the Hospital Anxiety and Depression Scale (HADS) questionnaire. 37 HADS scores were interpreted as no depression/anxiety (0-7), mild depression/anxiety (8-10), moderate depression/anxiety (11)(12)(13)(14) and severe depression/ anxiety (15)(16)(17)(18)(19)(20). Severity of Alopecia Tool (SALT) 38 scores were calculated to assess severity of hair loss, and patients were stratified accordingly: inactive disease (S0), patchy hair loss (S3 ≥ S4a), severe hair loss (S4b ≥ S5, alopecia universalis and totalis).…”

Section: Clinical Datamentioning

confidence: 99%

“…IFN‐γ and interleukin (IL)‐15 are crucial for potentiating the activity of CD8 + T cells and natural killer cells in AA . Concentrations of circulating IL‐6, tumour necrosis factor (TNF)‐α, IL‐17A, IL‐21, IL‐22 and IL‐23 are elevated in patients with AA . In the skin, molecular profiling reveals dysregulation in cytokines associated with type 1 and type 2 inflammation, while also indicating altered expression of IL‐23 .…”

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confidence: 99%

Alopecia areata is characterized by dysregulation in systemic type 17 and type 2 cytokines, which may contribute to disease‐associated psychological morbidity

et al. 2019

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Summary Background Alopecia areata (AA) is a common autoimmune disease, causing patchy hair loss that can progress to involve the entire scalp (totalis) or body (universalis). CD8+NKG2D+ T cells dominate hair follicle pathogenesis, but the specific mechanisms driving hair loss are not fully understood. Objectives To provide a detailed insight into the systemic cytokine signature associated with AA, and to assess the association between cytokines and depression. Methods We conducted multiplex analysis of plasma cytokines from patients with AA, patients with psoriatic arthritis (PsA) and healthy controls. We used the Hospital Anxiety and Depression Scale (HADS) to assess the occurrence of depression and anxiety in our cohort. Results Our analysis identified a systemic inflammatory signature associated with AA, characterized by elevated levels of interleukin (IL)‐17A, IL‐17F, IL‐21 and IL‐23 indicative of a type 17 immune response. Circulating levels of the type 2 cytokines IL‐33, IL‐31 and IL‐17E (IL‐25) were also significantly increased in AA. In comparison with PsA, AA was associated with higher levels of IL‐17F, IL‐17E and IL‐23. We hypothesized that circulating inflammatory cytokines may contribute to wider comorbidities associated with AA. Our assessment of psychiatric comorbidity in AA using HADS scores showed that 18% and 51% of people with AA experienced symptoms of depression and anxiety, respectively. Using linear regression modelling, we identified that levels of IL‐22 and IL‐17E are positively and significantly associated with depression. Conclusions Our data highlight changes in both type 17 and type 2 cytokines among people with AA, suggesting that complex systemic cytokine profiles may contribute both to the pathogenesis of AA and to the associated depression. What's already known about this topic? NKG2D+CD8+ T cells cause hair loss in alopecia areata (AA) but the immunological mechanisms underlying the disease are not fully understood. AA is associated with changes in levels of interleukin (IL)‐6, tumour necrosis factor‐α, IL‐1β and type 17 cytokines. Psychiatric comorbidity is common among people with AA. What does this study add? People with AA have increased plasma levels of the type 2 cytokines IL‐33, IL‐31 and IL‐17E (IL‐25), in addition to the type 17 cytokines IL‐17A, IL‐21, IL‐23 and IL‐17F. Levels of IL‐17E and IL‐22 positively predict depression score. What is the translational message? AA is associated with increased levels of multiple inflammatory cytokines, implicating both type 17‐ and type 2 immune pathways. Our data indicate that therapeutic strategies for treating AA may need to address the underlying type 17‐ and type 2 immune dysregulation, rather than focusing narrowly on the CD8+ T‐cell response. An immunological mechanism might contribute directly to the depression observed in people with AA.

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“… In contrast, studies in humans have shown an increase in T reg. However, the majority of studies in humans have been conducted via flow cytometry on peripheral blood . There are limited data addressing T reg in the local cutaneous environment.…”

Section: Introductionmentioning

confidence: 99%

Regulatory T‐cells in alopecia areata

et al. 2019

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Background Alopecia areata (AA) is believed to have an autoimmune mechanism in which the hair follicles are targeted by CD4+ and CD8+ lymphocytes. Studies investigating the autoimmune mechanism of other cutaneous diseases, including vitiligo, showed that Treg is a component of cutaneous immune privilege. Our study uses immunohistochemical staining in formalin‐fixed, paraffin‐embedded tissue to examine the percentage of CD4+FoxP3+, CD25+FoxP3+, and CD8+FoxP3+ Treg in AA in human specimens. Methods Immunohistochemical double staining for CD4+FoxP3+, CD25+FoxP3+, and CD8+FoxP3+ was performed on 12 AA cases and 12 other autoimmune and non‐autoimmune cutaneous diseases. The frequency of CD4+FoxP3+, CD25+FoxP3+, and CD8+ FoxP3+ Treg was counted and expressed as a percentage of total CD4+, CD25+, and CD8+ lymphocytes, respectively, in order to account for intersample inflammatory response variability. Results There was a significant reduction in the mean frequency of CD4+ FoxP3+ and CD25+ FoxP3+ in AA when compared to other autoimmune and non‐autoimmune cutaneous diseases. Conclusion Treg is significantly lower in AA when compared to other cutaneous diseases. Additionally, this immunohistochemical‐staining protocol may be useful to evaluate Treg in formalin‐fixed, paraffin‐embedded specimens for other cutaneous diseases. Studies examining Treg in AA and other cutaneous diseases may have implications for future interventions.

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Role of T helper 17 cells and T regulatory cells in alopecia areata: comparison of lesion and serum cytokine between controls and patients

Abstract: These results showed significantly high Th17 cytokines in both lesion and serum in AA patients, which may highlight a functional role of these cytokines in the pathogenesis of AA.

Cited by 62 publications

References 20 publications

IL‐17 and its role in inflammatory, autoimmune, and oncological skin diseases: state of art

IL‐17 and its role in inflammatory, autoimmune, and oncological skin diseases: state of art

Alopecia areata is characterized by dysregulation in systemic type 17 and type 2 cytokines, which may contribute to disease‐associated psychological morbidity

Regulatory T‐cells in alopecia areata

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