TABLE 3.

Summary of major post-translational modifications involved in AD.

PTMs	Factors	Expression	Subjects	Process participation	Functions	Reference
Phosphorylation	ERK	↑	Human AD	Increase IL-9, IL-33, and TSLP; activate NK-κB and STAT1 signaling; inhibit FLG induction	Promote inflammation; amplify the TH2 responses; disrupt barrier	Jang et al. (2013), Meephansan et al. (2013), Hong et al. (2015), Yi et al. (2017), Cha et al. (2019b), Park et al. (2019), Choi et al. (2021), Zhang et al. (2021), Zeze et al. (2022)
			Animal: DNFB-induced mice, MC903-induced mice
			NC/Nga mice
			Cell: HaCaT, NHEK
	p38	↑	Human AD	Upregulate FcεRI, IL-33; inhibit ZO-1 and RhoA	Increase antigen-sensitivity; trigger TH2 immune response; disrupt barrier	Meephansan et al. (2013), Song et al. (2015), Kanemaru et al. (2017)
			Cell: NHEK
	JNK	↑	Human AD	Increase TSLP; inhibit FLG and LOR induction	Promote inflammation; disrupt barrier	Kim et al. (2011), Jang et al. (2013), Cha et al. (2019a), Zhang et al. (2021)
			Animal: DNCB-induced mice
			Cell: HaCaT, NHEK
	AKT	↑	Human AD	Increase inflammatory cytokines, reduce FLG, LOR, INV, claudin1	Promote skin inflammation; promote hyperproliferation; disrupt barrier	Yang et al. (2014b), Naeem et al. (2017), Xiao et al. (2017), Jia and Zeng (2020), Hu et al. (2021), Mercurio et al. (2021)
			Animal: DfE-induced mice, oxazolone-induce mice
			Cell: HaCaT, rat epidermal keratinocytes
	AMPK	↑	Animal: MC903-induced mice	Inhibit NK-κB and mTOR signaling; suppress KC hyperproliferation	Suppress skin inflammation; suppress hyperproliferation	Hou et al. (2020), Crane et al. (2021), Dong et al. (2022)
			Cell: co-culture of primary human dermal fibroblasts and eosinophils, PAM212 cells
	Ribosomal protein S6	↑	Human AD	Increase inflammatory cytokines and KCs differentiation	Promote skin inflammation	Ruvinsky and Meyuhas (2006), Ruf et al. (2014)
	L-plastin	↑	Human AD	Enhance eosinophil migration	Promote skin inflammation	Pazdrak et al. (2011), Noh et al. (2016)
			Cell: EoL-1 cells
	HSP 27	↑	Human AD	Promote KC differentiation and FLG processing	Improve barrier formation	(O’Shaughnessy et al., 2007; Jonak et al., 2011; Niiyama et al., 2016)
Acetylation	HDAC3	↑	Animal: DNFB-induced mice	Active MCP1	Promote skin inflammation	Kim et al. (2012)
			Cell: RBL2H3 cells, mast cell
	HDAC6	↑	Animal: DNCB-induced mice, TNCB-induced mice	Increase CD8+ T cell inflammation	Promote skin inflammation	Tsuji et al. (2015), Kwon et al. (2021)
			Cell: HaCaT, co-culture of mouse skin dermal fibroblast cells and mast cells
	SIRT1	↓	Human AD	Suppress inflammatory cytokines; deacetylate NF-κB; promote FLG expression	Suppress skin inflammation; improve barrier dysfunction	Kauppinen et al. (2013), Ming et al. (2015), Lee et al. (2016), Kwon et al. (2021)
			Animal: DNCB-induced mice, ovalbumin
			-induced mice
			Cell: HaCaT
Ubiquitination	TRIM32	↓	Human AD	Ubiquitinate PKCζ and inactivate NF-κB and TLR signaling	Restrain TH2 differentiation	Liu et al. (2017), Wang et al. (2021)
			Animal: MC903-induced mice
	ITCH	↓	Animal: itchy mice	Ubiquitinate Tab1 and JunB; inhibit p38α phosphorylation	Restrain TH2 differentiation	(Fang et al., 2002; Theivanthiran et al., 2015)
	TMEM79	↓	Animal: flaky tail mice	Inhibit Wnt/Frizzled signaling	Maintain skin barrier integrity	(Sasaki et al., 2013; Saunders et al., 2013; Chen et al., 2020)
	c-CBL	↑	Human AD	Ubiquitinate PTKs; inhibit TCR signal transduction	Promote T-cell apoptosis	Loeser and Penninger (2007a), Mohapatra et al. (2013a), Salva et al. (2017)
			Cell: human CTCL cells
	Sharpin	↓	Human AD	Inactivate IL-33/ST2, NF-κB, and JAK/STAT signaling; suppress FLG expression	Restrain TH2 immune Response improve barrier dysfunction	(Tang et al., 2018; Sundberg et al., 2020)
			Animal: mouse
			Cell: HaCaT
	A20	↓	Human AD	Ubiquitinate IκBα; inhibit NF-κB activation	Suppress skin inflammation; restrain TH2 differentiation	G’Sell et al. (2015), Devos et al. (2019), Harirchian et al. (2019)
			Animal: mouse
			Cell: NHEK
SUMOylation	SUMO1	↓	Human AD	Targeted by miRNA-146a	Promote skin inflammation	Yan et al. (2019b)
			Animal: DNCB-induced mice
			Cell: 293T cells
	PIAS1	↓	Animal: AD dogs	Restrict Tregs differentiation	Suppress skin inflammation	Majewska et al. (2016)
Glycosylation	PGM3	↓	Human	Decrease IgE levels and TH2/TH17 cytokines	Suppress allergic response	Zhang et al. (2014)
	β-N-acetylglucosamine	↑	Animal: epicutaneous infection mice	Trigger Staphylococcus aureus	Induce skin inflammation	van Dalen et al. (2019)
			Cell: MUTZ-3-derived LCs, primary human LCs
Glycation	RAGE	↑	Animal: DfE- induced mice, DNCB-induced mice	Activate NF-κB phosphorylation	Promote skin inflammation	Karuppagounder et al. (2015), Wang et al. (2018)

Abbreviations: A20, Zinc finger protein A20; AD, atopic dermatitis; AGE, advanced glycation end products; AKT, protein kinase B; AMPK, AMP-activated protein kinase; c-CBL, casitas B-lineage lymphoma; CTCL, cutaneous T-cell lymphoma; DfE, dermatophagoides farina extract; DNCB, 2,4-dinitrochlorobenzene; ERK, extracellular signal-regulated protein kinase; FLG, filaggrin; HDAC, histone deacetylase; Hsp, heat shock proteins 27; IL, interleukin; INV, involucrin; JAK, janus kinase; JNK, c-Jun N-terminal kinases; KC, keratinocytes; LC, langerhans cells; LOR, loricrin; MC903, calcipotriol; MCP1, monocyte chemoattractant protein; NHEL, normal human epidermal keratinocyte; SIRT1, sirtuin1; PGM3, phosphoglucomutase3; PIAS1, protein inhibitor of activated STAT1; PKCζ, protein kinase C zeta; PTK, protein tyrosine kinase; RAGE, receptor for AGEs; STAT, signal transducer and activator of transcription; STAT, signal transducer and activator of transcription; SUMO, small ubiquitin like modifier; Tab1, TGF-β activated kinase 1; T_H2, T helper 2 cell; TNCB, 2, 4, 6-trinitrochlorobenzene; TLR, toll-like receptor; TMEM79, transmembrane protein 79; Trim32, tripartite motif 32; TSLP, thymic stromal lymphopoietin.