title: TIPE2 Alleviates Systemic Lupus Erythematosus Through Regulating Macrophage Polarization.
abstract: OBJECTIVE
  We have recently shown that macrophage polarization may alter the pathogenesis and severity of systemic lupus erythematosus (SLE). However, a practical approach to modulate macrophage polarization in vivo is so far not available. In the current study, we aimed to use tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2) to regulate macrophage polarization in vitro and in vivo, and to study the effects on experimental SLE.
  
  
  METHODS
  We prepared adeno-associated virus carrying TIPE2 (AAV-TIPE2). We induced experimental SLE in mice with an activated lymphocyte-derived DNA (ALD-DNA) method. We examined the effects of TIPE2 overexpression on macrophage polarization in vitro, and in vivo in the SLE model. We also examined the effects of TIPE2 overexpression on the severity of SLE, by serum anti-dsDNA autoantibody, renal pathological changes, and urine protein levels.
  
  
  RESULTS
  ALD-DNA induced SLE-like features in mice, manifested by induction of serum anti-dsDNA autoantibody, renal pathological changes, and increases in urine protein levels. TIPE2 overexpression by AAV-TIPE2 induced macrophage polarization to a M2 phenotype, in vitro and in vivo in the SLE mouse model. TIPE2 overexpression significantly decreased SLE severity.
  
  
  CONCLUSIONS
  TIPE2 alleviates experimental SLE through induction of macrophage polarization to a M2 phenotype, which may be used as a promising therapeutic strategy for treating SLE.
authors.affiliation: Department of Dermatology, Affiliated Huashan Hospital of Fudan University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhu
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Yang
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.forename: Jinhua
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism / Q000473:pathology*; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D012720:Severity of Illness Index
chemical_list: D000974:Antibodies, Antinuclear; D047908:Intracellular Signaling Peptides and Proteins; C529002:TIPE2 protein, mouse