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IL‐12 and IL‐23 induce distinct types of EAE based on histological features and chemokine expression in the CNS
Author(s) -
Kroenke Mark A,
Carlson Thaddeus J,
Andjelkovic Anuska V,
Segal Benjamin M
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.456
Subject(s) - experimental autoimmune encephalomyelitis , adoptive cell transfer , chemokine , immunology , cxcl1 , cxcl2 , biology , autoimmunity , cxcl10 , inflammation , cytokine , t cell , chemokine receptor , immune system
The IL‐12 p40 family of cytokines (composed of IL‐12 and IL‐23) plays a critical role in the development of experimental autoimmune encephalomyelitis (EAE). However, the relative contributions of IL‐12 and IL‐23 to the pathogenic process remain to be elucidated. Here we show that polarization of uncommitted myelin‐reactive T cells in the presence of either IL‐12 or IL‐23 confers encephalogenicity. Adoptive transfer of Th1 or Th17 polarized cells into naïve syngeneic hosts resulted in an ascending paralysis that was clinically indistinguishable. However, histological and RT‐PCR analysis of central nervous system (CNS) tissues revealed remarkable qualitative differences in the type of inflammation mediated by each cell type. While Th1 induced disease was characterized by a macrophage rich CNS infiltrate, neutrophils were a prominent component of Th17 induced lesions. Consistent with these findings, the monocyte attracting chemokines CXCL9‐11 were preferentially upregulated in the CNS of mice injected with Th1 effectors, whereas the neutrophil attracting chemokines CXCL1 and CXCL2 were upregulated in the CNS mice given Th17 effectors. Treatment with anti‐IL‐17 was effective in inhibiting EAE induced by transfer of Th17, but not Th1, cells. These findings indicate that autoimmunity can be mediated by distinct effector cells that employ disparate immunological pathways to achieve a similar clinical outcome.