title: Hsp65-producing Lactococcus lactis prevents experimental autoimmune encephalomyelitis in mice by inducing CD4+LAP+ regulatory T cells.
abstract: Heat shock proteins (Hsps) participate in the cellular response to stress and they are hiperexpressed in inflammatory conditions. They are also known to play a major role in immune modulation, controlling, for instance, autoimmune responses. In this study, we showed that oral administration of a recombinant Lactococcus lactis strain that produces and releases LPS-free Hsp65 prevented the development of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. This was confirmed by the reduced inflammatory cell infiltrate and absence of injury signs in the spinal cord. The effect was associated with reduced IL-17 and increased IL-10 production in mesenteric lymph node and spleen cell cultures. Hsp65-producing-L. lactis-fed mice had a remarkable increase in the number of natural and inducible CD4+Foxp3+ regulatory T (Treg) cells and CD4+LAP+ (Latency-associated peptide) Tregs - which express the membrane-bound TGF-β - in spleen, inguinal and mesenteric lymph nodes as well as in spinal cord. Moreover, many Tregs co-expressed Foxp3 and LAP. In vivo depletion of LAP+ cells abrogated the effect of Hsp65-producing L. lactis in EAE prevention and worsened disease in medium-fed mice. Thus, Hsp65-L.lactis seems to boost this critical regulatory circuit involved in controlling EAE development in mice.
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Rafael M
authors.initials: RM
authors.lastname: Rezende
authors.forename: Rafael P
authors.initials: RP
authors.lastname: Oliveira
authors.forename: Samara R
authors.initials: SR
authors.lastname: Medeiros
authors.forename: Ana C
authors.initials: AC
authors.lastname: Gomes-Santos
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Alves
authors.forename: Flávia G
authors.initials: FG
authors.lastname: Loli
authors.forename: Mauro A F
authors.initials: MA
authors.lastname: Guimarães
authors.forename: Sylvia S
authors.initials: SS
authors.lastname: Amaral
authors.forename: André P
authors.initials: AP
authors.lastname: da Cunha
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
authors.forename: Vasco
authors.initials: V
authors.lastname: Azevedo
authors.forename: Anderson
authors.initials: A
authors.lastname: Miyoshi
authors.forename: Ana M C
authors.initials: AM
authors.lastname: Faria
mesh_terms: D000818:Animals; D015551:Autoimmunity; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism; D018834:Chaperonin 60 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D013294:Lactococcus lactis / Q000235:genetics / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009166:Mycobacterium leprae / Q000235:genetics*; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
chemical_list: D001426:Bacterial Proteins; D015704:CD4 Antigens; D018834:Chaperonin 60; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016212:Transforming Growth Factor beta; C074119:heat-shock protein 65, Mycobacterium