title: Blockade of macrophage autophagy ameliorates activated lymphocytes-derived DNA induced murine lupus possibly via inhibition of proinflammatory cytokine production.
abstract: OBJECTIVE
  Systemic lupus erythematosus (SLE) is a typical inflammatory autoimmune disease for its unknown pathogenesis and potential fatality. It has been reported that autophagy has a crosstalk with autoimmunity, but its impact on the pathogenesis of SLE remains unclear. Here, we investigated the role of autophagy in inflammatory response of macrophages under SLE conditions.
  
  
  METHODS
  First, we detected the expression of autophagy-related genes (Atg5, Atg12 and Beclin 1) in the macrophages derived from activated lymphocytes-derived DNA (ALD-DNA) induced murine lupus as well as in the PBMC from SLE patients. And then through adoptive transfer of Beclin 1 knockdown macrophages, we further investigated the potential effect of macrophage autophagy on the SLE-associated inflammatory response and disease severity by evaluating serum anti-dsDNA antibodies and proteinuria levels, immune complex deposition as well as renal pathological changes.
  
  
  RESULTS
  We found that autophagy related genes were significantly upregulated in the splenic and renal macrophages of lupus mice and in the PBMC of SLE patients. Adoptive transfer of Beclin 1 knockdown macrophages could significantly decrease the anti-dsDNA antibodies and proteinuria levels, robustly reduce renal immune complex deposition and remit glomerulonephritis, indicating the amelioration of murine lupus. This protective effect was associated with the obviously decreased production of proinflammatory cytokines IL-6 and TNF-α.
  
  
  CONCLUSIONS
  Our results suggested that aberrant activated autophagy in macrophages contributed to the pathogenesis of murine lupus possibly via promoting the production of proinflammatory cytokines TNF-α and IL-6, and inhibition of autophagy might represent a novel regulation strategy for excessive activation of proinflammatory macrophages and a new therapeutic regime for SLE.
authors.affiliation: Jiangsu Provincial Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Science, Soochow University, Suzhou, China. rainpeerless@126.com.
authors.forename: Baihui
authors.initials: B
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Yue
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Dong
authors.forename: Yongbing
authors.initials: Y
authors.lastname: Shi
authors.forename: Sidong
authors.initials: S
authors.lastname: Xiong
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000235:genetics; D001343:Autophagy / Q000235:genetics; D000071186:Beclin-1; D016022:Case-Control Studies; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D004247:DNA / Q000276:immunology / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000235:genetics; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D051379:Mice; D008807:Mice, Inbred BALB C; D012720:Severity of Illness Index; D013997:Time Factors; D014162:Transfection
chemical_list: D000974:Antibodies, Antinuclear; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D016207:Cytokines; D018836:Inflammation Mediators; D004247:DNA