The Keratinocyte as a Crucial Cell in the Predisposition, Onset, Progression, Therapy and Study of the Atopic Dermatitis
Abstract
:1. Introduction
2. Keratinocyte in Skin Homeostasis
2.1. Proliferation Phase
2.2. Maturation Phase
2.3. Cornification Phase
3. Participation of Keratinocyte in Predisposition, Onset and Progression of the Atopic Dermatitis
3.1. Genetic Background of the Keratinocyte Predisposing to Atopic Dermatitis
Structural Genes | |||||
---|---|---|---|---|---|
Gene | Polymorphism/ Mutations | Mechanism | Prevalent Populations | OR | Reference |
FLG | P478S | Prevents the protease cleavage through serine phosphorylation, and then affects the FLG aggregation to keratin filaments | Asian (Taiwan) Asian (Korean) | 5.67 1.877 | [115,116] |
3321delA | Premature termination codon 41 bases downstream that stops protein translation in filaggrin repeat domain 2 | Asian | 3.54 | [112,117] | |
S2554X, S2889X, S3296X, K4022X, R501X | Nonsense mutations | Asian | 3.54 | [112,117] | |
2282del4 | Deletion of four base pairs that results in a premature stop codon and complete loss of FLG production | Northern European European American African American | NR 5.6 2.5 | [118,119] | |
Innate immune response | |||||
TLR2 | R753Q | Alteration of the function of the intracellular signaling portion homologous to the IL-1 receptor designated as Toll/IL-1 receptor (TIR) domain. | German Italian | NR NR | [120] |
R677W | Associated with reduced NF-κB activation and to increase the risk of bacterial infection | [121] | |||
TLR4 | D299G | Impaired dimerization of TLR4 and MD-2 in presence of ligand | Italian | 2.46 | [122,123] |
DEFB1 | A692G | Generates an NF-kB transcription factor-binding sequence in the position -20 of the 5′ untranslated region (5′ UTR) with a plausible effect on the expression of hBD2 | Mexican | 3.21 | [124] |
G1654A | In exon 2, meaning a changed Val37Ile next to six conserved cysteine residues that could affect its folding | Mexican | 17.37 | [124] | |
TSLP | rs11466749 | Means a change 813A/G | European American | 0.6 | [125,126] |
rs10043985 | Means a change 597T/C | African American | 0.5 | [125,127] | |
rs2289276 | Means a change 1350C/T | American African | 1.8 | [125,127] |
3.2. The Keratinocyte in the Primary Origin of Atopic Dermatitis
3.3. Involvement of Keratinocytes in Acute Lesions
3.4. Chronic Lesions and KC Participation
3.5. Bidirectional Communication between Keratinocyte and Microbiota
4. The Use of the Keratinocyte as an In Vitro Model of Atopic Dermatitis
5. Pharmacological Therapy to Restore Keratinocytes
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gallegos-Alcalá, P.; Jiménez, M.; Cervantes-García, D.; Salinas, E. The Keratinocyte as a Crucial Cell in the Predisposition, Onset, Progression, Therapy and Study of the Atopic Dermatitis. Int. J. Mol. Sci. 2021, 22, 10661. https://doi.org/10.3390/ijms221910661
Gallegos-Alcalá P, Jiménez M, Cervantes-García D, Salinas E. The Keratinocyte as a Crucial Cell in the Predisposition, Onset, Progression, Therapy and Study of the Atopic Dermatitis. International Journal of Molecular Sciences. 2021; 22(19):10661. https://doi.org/10.3390/ijms221910661
Chicago/Turabian StyleGallegos-Alcalá, Pamela, Mariela Jiménez, Daniel Cervantes-García, and Eva Salinas. 2021. "The Keratinocyte as a Crucial Cell in the Predisposition, Onset, Progression, Therapy and Study of the Atopic Dermatitis" International Journal of Molecular Sciences 22, no. 19: 10661. https://doi.org/10.3390/ijms221910661