T cell immunoglobulin and mucin domain-containing protein 3 inhibits interleukin-12 secretion by CD14+ monocytes from patients with psoriasis vulgaris / 中华皮肤科杂志

ABSTRACT

Objective To assess the role of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) in regulation of interleukin(IL)-12 secretion by CD14+ peripheral blood monocytes from patients with psoriasis vulgaris.Methods From November 2017 to March 2018,a total of 47 patients with psoriasis vulgaris (psoriasis group) and 19 healthy volunteers (control group) were enrolled from Shanxi Provincial People's Hospital.Peripheral blood mononuclear cells (PBMC) were isolated,and stimulated with Toll-like receptor (TLR) ligands.TIM-3 expression and IL-12 secretion by CD14+ monocytes were measured by flow cytometry.After blockade of TIM-3 pathway by anti-TIM-3 neutralizing antibody,changes in the downstream signaling pathway molecules in and IL-12 secretion by CD14+ monocytes were investigated.Two independent samples t-test was used for comparison between two groups,and Pearson correlation test for correlation analysis.Results Under the unstimulated condition,the level of IL-12 secreted by CD14+ monocytes was very low,and the proportion of CD14+TIM-3+ cells was significantly higher in the psoriasis group (12.20％ ± 2.83％) than in the control group (9.91％ ± 1.77％,t =3.270,P =0.001 7).After the stimulation with TLR ligands,the proportion of CD14+IL-12+ cells was significantly lower in the psoriasis group (13.49％ ± 2.80％) than in the control group (28.97％ ± 8.97％,t =10.71,P ＜0.000 1),but the proportion of CD14+TIM-3+ cells was still higher in the psoriasis group (6.80％ ± 1.11％)than in the control group (4.85％ ± 1.37％,t =6.064,P ＜ 0.000 1).The proportion of CD14+TIM-3+ cells was negatively correlated with that of CD14+IL-12+ cells in both the control group and psoriasis group (r =-0.473,-0.371 respectively,both P ＜ 0.05).The TIM-3 pathway blockade could induce the decrease of suppressor of cytokine signaling 1 in CD14+ monocytes,increase the phosphorylation of signaling transducers and activators of transcription 1,and promote IL-12 secretion by CD 14+ monocytes induced by keratinocytes isolated from psoriatic skin lesions.Conclusion TIM-3 plays a crucial role in the negative regulation of CD 14+ monocyte-induced innate immune response in psoriasis.