TABLE 1.
Functional mechanisms of known inflammatory mediators in HF development and specific expression patterns in aging dWAT.
| Cytokines | Properties related to HF | References | Expression patterns in dWAT_FPKM |
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| Gene | OTD | YTD | |||
| TNF-a | Have significant positive association with AA; is required for normal cell death of HF and anagen-catagen transition in mice; Injection of TNF-a leads to apoptosis of HF bulb matrix keratinocytes in mice. TNF-a also inhibits HF elongation in a dose-dependent manner. K14-TNF alpha transgenic mice exerted impaired HF growth. | Cheng et al. 1992; Philpott et al. 1996b; Soma et al., 1998; Ruckert et al., 2000; Tong and Coulombe 2006; Perez-Garijo et al. 2013; Atwa et al. 2016 | Tnfaip6 Tnfrsf13b Tnfaip8l2 Tnfsf13 Tnfaip3 Tnfrsf10b Tnfrsf11a Tnfrsf1b Tnfsf10 Tnfrsf14 Tnfsf12 Tnfrsf26 |
9.95549 1.87504 7.895 11.0502 3.83357 2.64808 2.01242 10.7332 9.14176 2.82864 39.4577 1.20813 |
1.71115 0.630668 5.12489 5.9425 1.64293 1.14413 1.15726 6.5328 5.90121 1.09449 29.5722 0.199513 |
| IL-6 | IL-6 KO mice resulted in STAT3 pathway activation and enhanced wound-induced hair neogenesis; DP cells secreted IL-6 in response to dihydrotestosterone. | Yu et al. 2008; Kwack et al. 2012; Nelson et al. 2016 | Il6st Il6 Il6ra |
111.495 6.19491 7.08773 |
72.9043 0.224645 5.37911 |
| IL-1a/b | Act as a crucial mediator inducing HF regression. Upregulation of IL1 leads to diminished and atrophic hair follicles; IL-1a and IL-1b inhibit HF growth in organ culture; IL1 transgenic mice were characterized by hair loss and focal skin inflammation. | Harmon and Nevins 1993; Groves et al. 1995; Philpott et al. 1996a; Hoffmann et al. 1997; Hoffmann et al. 1998 | Il1a Il1b Il1rap Il1r1 Il1r2 Il1rn Il1rl2 |
0.514973 3.36946 2.6094 11.1733 9.15598 2.50242 5.44209 |
0.0371823 0.739462 2.00408 7.76998 6.54273 1.32742 3.64348 |
| IL16 | Its polymorphisms may play a role in AA; | Lew et al. 2014 | Il16 | 3.20473 | 1.97227 |
| IL-7 | IL-7 derived from HF are required for homeostasis of CD4(+) and CD8(+) skin-resident memory T cells | Adachi et al. 2015 | Il7 Il7r |
2.87597 2.72528 |
0.598882 0.162671 |
| IFN-gamma | An important inducer of catagen in HF; its upregulation can result in the collapse of immune privilege of HF | Ito et al. 2005; Harries et al. 2013; Ito 2013; Ryu et al. 2014 | Ifnar2 Ifngr1 |
36.3087 55.3079 |
23.0931 40.3651 |
| Cxcr3 | Overexpressed on alopecic effector T cells and its ablation prevents AA onset; Deficiency in cxcR3 impaired the patterning of primary hair placodes. | Lefebvre et al. 2012; Dai et al. 2016 | Cxcr3 | 1.09397 | 0.289984 |
| CXCL9/10/11 | Significantly upregulated in AA lesions and promoted AA progression. | Suarez-Farinas et al. 2015; Dai et al. 2016 | Cxcl9 Cxcl10 Cxcl11 | 2.91259 7.33465 0.0975968 |
1.33173 4.84593 0.0488607 |
| Cxcl1/2 | Cxcl1/2 are associated with AA susceptibility | Kim et al. 2015 | Cxcl1 | 15.1405 | 0.108917 |
| Cxcl2 | 0.781783 | 0.158399 | |||
| Ccl2 | Plucking HFs released Ccl2 to signal to neighboring unplucked HFs, activating HFSCs for regeneration; the isthmus of HF expressed CCL2 to promote the recruitment of Langerhans cells into skin | Nagao et al. 2012; Chen et al., 2015 | Ccl2 | 15.5977 | 5.95203 |
| CCL8 | HF bugle region produced CCL8 which inhibit the recruitment of Langerhans cells into the skin | Nagao et al. 2012 | Ccl8 | 269.611 | 87.7888 |