The Role of T Helper 22 Cells in Dermatological Disorders

Pan, Yu; Du, Dan; Wang, Lian; Wang, Xiaoyun; He, Gu; Jiang, Xian

doi:10.3389/fimmu.2022.911546

Cited by 12 publications

(8 citation statements)

References 258 publications

(369 reference statements)

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“…The main secretion of Th22 is IL-22 [ 30 ]. Moreover, studies have shown that IL-22 can promote the proliferation of keratinocytes, inhibit their differentiation, promote the expression of related keratin, control hair follicle circulation, and promote hair growth [ 31 – 33 ].…”

Section: Resultsmentioning

confidence: 99%

Th22 is the effector cell of thymosin β15-induced hair regeneration in mice

Tao,

Ying,

et al. 2024

Inflamm Regener

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Background Thymosin beta family has a significant role in promoting hair regeneration, but which type of T cells play a key role in this process has not been deeply studied. This research aimed to find out the subtypes of T cell that play key role in hair regeneration mediated by thymosin beta 15 (Tβ15). Methods Ready-to-use adenovirus expressing mouse Tmsb15b (thymosin beta 15 overexpression, Tβ15 OX) and lentivirus-Tβ15 short hairpin RNA (Tβ15 sh) were used to evaluate the role of Tβ15 in hair regeneration and development. The effect of Th22 cells on hair regeneration was further studied by optimized Th22-skewing condition medium and IL-22 binding protein (IL-22BP, an endogenous antagonist of IL-22, also known as IL-22RA2) in both ex vivo culture C57BL/6J mouse skin and BALB/c nude mice transplanted with thymus organoid model. Results The results show that Tβ15, the homologous of Tβ4, can promote hair regeneration by increasing the proliferation activity of hair follicle cells. In addition, high-level expression of Tβ15 can not only increase the number of Th22 cells around hair follicles but also accelerate the transformation of hair follicles to maturity. Consistent with the expected results, when the IL-22BP inhibitor was used to interfere with Th22, the process of hair regeneration was blocked. Conclusions In conclusion, Th22 is the key effector cell of Tβ15 inducing hair regeneration. Both Tβ15 and Th22 may be the potential drug targets for hair regeneration.

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Section: Resultsmentioning

confidence: 99%

Th22 is the effector cell of thymosin β15-induced hair regeneration in mice

Tao,

Ying,

et al. 2024

Inflamm Regener

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“…Significantly higher amounts of IL-22-producing T cells are distinct in AD patients [ 30 ]. Keratinocytes express IL-22 receptors widely, and studies have shown that IL-22-keratinocyte crosstalk plays an essential role in skin barrier defense and AD pathogenesis [ 31 ]. Real-time PCR data revealed that the most prominent gene activation of Th22 immune pathways was found in skin samples of the acute phase and then progressively increased during the chronic phase of the disease [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Investigating Vα7.2+/CD161− T Cell and MAIT Cell Profiles Using Flow Cytometry in Healthy Subjects and Subjects with Atopic Dermatitis

Singh,

Gaspar,

Szegedi

et al. 2024

IJMS

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This study investigates the roles of mucosal-associated invariant T (MAIT) cells and Vα7.2+/CD161− T cells in skin diseases, focusing on atopic dermatitis. MAIT cells, crucial for bridging innate and adaptive immunity, were analyzed alongside Vα7.2+/CD161− T cells in peripheral blood samples from 14 atopic dermatitis patients and 10 healthy controls. Flow cytometry and machine learning algorithms were employed for a comprehensive analysis. The results indicate a significant decrease in MAIT cells and CD69 subsets in atopic dermatitis, coupled with elevated CD38 and polyfunctional MAIT cells producing TNFα and Granzyme B (TNFα+/GzB+). Vα7.2+/CD161− T cells in atopic dermatitis exhibited a decrease in CD8 and IFNγ-producing subsets but an increase in CD38 activated and IL-22-producing subsets. These results highlight the distinctive features of MAIT cells and Vα7.2+/CD161− T cells and their different roles in the pathogenesis of atopic dermatitis and provide insights into their potential roles in immune-mediated skin diseases.

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“…S100A proteins have proinflammatory functions, including chemotaxis of T‐cells 21 . Although S100A8 , S100A9 , and S100A12 expression is induced by both Th22 cytokine (IL‐22) and Th17 cytokine (IL‐17) signaling in AD skin, 22,23 IL‐22 acts via JAK1 signaling, whereas IL‐17 does not (Figure S5). 1,11 Therefore, abrocitinib, a JAK1 inhibitor, likely reduced S100A8 , S100A9 , and S100A12 expression by inhibiting IL‐22 signaling.…”

Section: Discussionmentioning

confidence: 99%

Effect of abrocitinib on skin biomarkers in patients with moderate‐to‐severe atopic dermatitis

Guttman‐Yassky,

Facheris,

Gomez‐Arias

et al. 2023

Allergy

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BackgroundThis is the first report on the effects of abrocitinib, a Janus kinase 1–selective inhibitor, on the expression of skin biomarkers in patients with moderate‐to‐severe atopic dermatitis (AD).MethodsJADE MOA (NCT03915496) was a double‐blind Phase 2a trial. Adults were randomly assigned 1:1:1 to receive monotherapy with once‐daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 weeks. The primary endpoint was change from baseline in markers of inflammation (matrix metalloproteinase [MMP]‐12), epidermal hyperplasia (keratin‐16 [KRT16]), T‐helper 2 (Th2) immune response (C‐C motif chemokine ligand [CCL]17, CCL18, and CCL26), and Th22 immune response (S100 calcium binding protein A8, A9, and A12 [S100A8, S100A9, and S100A12]) in skin through 12 weeks.ResultsA total of 46 patients received abrocitinib 200 mg (n = 14), abrocitinib 100 mg (n = 16), or placebo (n = 16). Abrocitinib improved AD clinical signs and reduced itch. Gene expression of MMP‐12, KRT16, S100A8, S100A9, and S100A12 was significantly decreased from baseline with abrocitinib 200 mg (at Weeks 2, 4, and 12) and abrocitinib 100 mg (at Weeks 4 and 12) in a dose‐dependent manner. Abrocitinib 200 mg resulted in significant decreases from baseline in CCL17 expression at Week 12 and CCL18 expression at Weeks 2, 4, and 12; no significant decreases were observed for CCL26.ConclusionsAlongside improvements in clinical signs and symptoms of AD, 12 weeks of abrocitinib treatment resulted in downregulation of genes associated with inflammation, epidermal hyperplasia, and Th2 and Th22 immune responses in the skin of patients with moderate‐to‐severe AD.

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The Role of T Helper 22 Cells in Dermatological Disorders

Cited by 12 publications

References 258 publications

Th22 is the effector cell of thymosin β15-induced hair regeneration in mice

Th22 is the effector cell of thymosin β15-induced hair regeneration in mice

Investigating Vα7.2+/CD161− T Cell and MAIT Cell Profiles Using Flow Cytometry in Healthy Subjects and Subjects with Atopic Dermatitis

Effect of abrocitinib on skin biomarkers in patients with moderate‐to‐severe atopic dermatitis

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