title: Caerulomycin A suppresses immunity by inhibiting T cell activity.
abstract: BACKGROUND
  Caerulomycin A (CaeA) is a known antifungal and antibiotic agent. Further, CaeA is reported to induce the expansion of regulatory T cell and prolongs the survival of skin allografts in mouse model of transplantation. In the current study, CaeA was purified and characterized from a novel species of actinomycetes, Actinoalloteichus spitiensis. The CaeA was identified for its novel immunosuppressive property by inhibiting in vitro and in vivo function of T cells.
  
  
  METHODS
  Isolation, purification and characterization of CaeA were performed using High Performance Flash Chromatography (HPFC), NMR and mass spectrometry techniques. In vitro and in vivo T cell studies were conducted in mice using flowcytometry, ELISA and thymidine-[methyl-(3)H] incorporation.
  
  
  RESULTS
  CaeA significantly suppressed T cell activation and IFN-γ secretion. Further, it inhibited the T cells function at G1 phase of cell cycle. No apoptosis was noticed by CaeA at a concentration responsible for inducing T cell retardation. Furthermore, the change in the function of B cells but not macrophages was observed. The CaeA as well exhibited substantial inhibitory activity in vivo.
  
  
  CONCLUSIONS
  This study describes for the first time novel in vitro and in vivo immunosuppressive function of CaeA on T cells and B cells. CaeA has enough potential to act as a future immunosuppressive drug.
authors.affiliation: Biochemical Engineering Research and Process Development Centre, CSIR-Institute of Microbial Technology, Chandigarh, India.
authors.forename: Arvind K
authors.initials: AK
authors.lastname: Singla
authors.affiliation: Immunology Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India.
authors.forename: Rama Krishna
authors.initials: RK
authors.lastname: Gurram
authors.affiliation: Immunology Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India.
authors.forename: Arun
authors.initials: A
authors.lastname: Chauhan
authors.affiliation: Experimental Animal Facility, CSIR-Institute of Microbial Technology, Chandigarh, India.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Khatri
authors.affiliation: Biochemical Engineering Research and Process Development Centre, CSIR-Institute of Microbial Technology, Chandigarh, India.
authors.forename: Rakesh M
authors.initials: RM
authors.lastname: Vohra
authors.affiliation: Department of Chemistry, CSIR-Institute of Microbial Technology, Chandigarh, India.
authors.forename: Ravinder S
authors.initials: RS
authors.lastname: Jolly
authors.affiliation: Immunology Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, India.
authors.forename: Javed N
authors.initials: JN
authors.lastname: Agrewala
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D065095:Calcineurin Inhibitors / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D005285:Fermentation; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011725:Pyridines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D011725:Pyridines; D016212:Transforming Growth Factor beta; C544423:caerulomycin A; D016753:Interleukin-10; D007371:Interferon-gamma