Treatment with TNF-α inhibitor rectifies M1 macrophage polarization from blood CD14+ monocytes in patients with psoriasis independent of STAT1 and IRF-1 activation

• Published in: Journal of dermatological science Vol. 91; no. 3; pp. 276 - 284
• Main Authors: Lin, Shang-Hung, Chuang, Hung-Yi, Ho, Ji-Chen, Lee, Chih-Hung, Hsiao, Chang-Chun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2018
• Subjects: Adalimumab - therapeutic use; Adult; Anti-Inflammatory Agents - therapeutic use; Case-Control Studies; Cell Plasticity - drug effects; Female; Humans; Interferon Regulatory Factor-1 - metabolism; IRF-1; Macrophage polarization; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Male; Middle Aged; Monocytes - drug effects; Monocytes - immunology; Monocytes - metabolism; Phenotype; Psoriasis; Psoriasis - drug therapy; Psoriasis - immunology; Psoriasis - metabolism; Severity of Illness Index; Signal Transduction - drug effects; STAT1; STAT1 Transcription Factor - metabolism; TNF-α inhibitor; Treatment Outcome; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - metabolism; U937 Cells; TNF-α; Psoriasis; Macrophage polarization; STAT1; IRF-1; CD14; TNF-α inhibitor
• ISSN: 0923-1811; 1873-569X
• DOI: 10.1016/j.jdermsci.2018.05.009

Psoriasis is a systemic inflammatory disease with dramatic responses to TNF-α inhibitors. TNF-α is mainly produced by macrophages. However, how macrophage polarization contributes to psoriasis remains unknown. We aimed to investigate the molecular mechanisms of macrophage polarization in psoriasis. 8 patients with moderate to severe psoriasis (Male/Female: 4/4, average age: 47.9 years old) and 8 healthy controls (Male/Female: 4/4, average age: 49.3 years old) were recruited. Their peripheral CD14+ monocytes were isolated with magnetic beads and then were differentiated into macrophages. The differential macrophage polarization was compared among normal controls, psoriatic patients before and after TNF-α inhibitors. The U937 cells were used to investigate the mechanisms by which TNF-α altered the macrophage polarization. The ratio of M1 to M2a macrophage polarization was higher in psoriatic patients comparing with that in controls. The decreasing M1/M2a ratio was parallel to decreasing PASI severity score after adalimumab treatment. Consistently, TNF-α blockage decreased M1/M2a ratio in U937 cells. The induction of STAT1 and IRF-1 in polarized U937 M1 cells was inhibited by TNF-α inhibitor. However, STAT1 and/or IRF-1 interference could not resume M1 polarization. In skin, the increased M1 and M2 infiltration in lesions returned to baseline after successful treatment with TNF-α inhibitor. Increased M1 polarization is associated with higher disease severity in psoriasis, resuming to baseline after successful treatment by TNF-α inhibitors. TNF-α blockage inhibits M1 polarization through STAT1- and IRF-1-independent pathways. Macrophage polarization may contribute to disease progression in psoriasis.