title: IL-10, IL-4, and STAT6 promote an M2 milieu required for termination of P0(106-125)-induced murine experimental autoimmune neuritis.
abstract: The role of the type 2 helper T cell (Th2)-polarizing cytokines IL-4 and IL-10 has not yet been studied in P0106-125-induced murine experimental autoimmune neuritis (EAN). We, therefore, addressed the functional relevance of these cytokines and signaling via the IL-4-associated transcription factor STAT6. The clinical course of P0106-125-induced EAN in mice deficient for IL-10(0/0), IL-4(0/0), or STAT6(0/0) was significantly aggravated compared with that of wild-type control mice. In addition, treatment of P0106-125-immunized C57BL/6 mice at the onset of clinical symptoms with a monoclonal IL-10 neutralizing antibody aggravated symptoms and prolonged disease to a similar degree as in IL-10(0/0) mice. This exacerbated course was attributed to a more prominent Th1 immune response associated with a persistent M1 milieu in the sciatic nerve and in the regional and systemic lymphatic system. These data suggest a Th2-polarized milieu being required to prevent axonal damage of the sciatic nerve and to terminate the P0106-125-specific immune response in EAN. Beyond the already known role of macrophages as pathogenic effector cells in EAN, these data suggest that M2-differentiated macrophages do not damage and may even protect neural tissues in EAN. Thus, these data highlight the pathogenetic relevance of the macrophage polarization status in EAN. Therapeutic modulation of immune responses from an M1 toward an M2 milieu may be a promising novel strategy in peripheral nervous system neuritis.
authors.affiliation: Department of Neuropathology, University Hospital of Cologne, Cologne, Germany. Electronic address: anna.brunn@uk-koeln.de.
authors.forename: Anna
authors.initials: A
authors.lastname: Brunn
authors.affiliation: Department of Neuropathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Mirna
authors.initials: M
authors.lastname: Mihelcic
authors.affiliation: Department of Neuropathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Mariana
authors.initials: M
authors.lastname: Carstov
authors.affiliation: Department of Neuropathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Lea
authors.initials: L
authors.lastname: Hummel
authors.affiliation: Department of Neuropathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Geier
authors.affiliation: Department of Neuropathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Department of Neuropathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Saupe
authors.affiliation: Institute for Medical Microbiology, Immunology, and Hygiene, Medical Center, Cologne, Germany; Center for Molecular Medicine Colgne, University of Cologne, Cologne, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Utermöhlen
authors.affiliation: Department of Neuropathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Deckert
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018993:Myelin P0 Protein / Q000378:metabolism; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D017933:Peripheral Nervous System / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D012584:Sciatic Nerve / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: C556062:IL10 protein, mouse; D018993:Myelin P0 Protein; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D016753:Interleukin-10; D015847:Interleukin-4