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Published online before print September 15, 2004

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(Journal of Leukocyte Biology. 2004;76:1118-1124.)
© 2004 by Society for Leukocyte Biology

Differential macrophage expression of IL-12 and IL-23 upon innate immune activation defines rat autoimmune susceptibility

Åsa Andersson^*,1, Riikka Kokkola, Judit Wefer^*, Helena Erlandsson-Harris and Robert A. Harris^*

^* Departments of Clinical Neurosciences, Applied Immunology, Karolinska Hospital, and
Medicine, Rheumatology Unit, Karolinska Institutet at Karolinska Hospital, Stockholm, Sweden

¹ Correspondence: Applied Immunology Unit, CMM L8:04, Karolinska Sjukhuset, S-171 76 Stockholm, Sweden. E-mail: Asa.Andersson{at}cmm.ki.se

Rodents typically demonstrate strain-specific susceptibilities to induced autoimmune models such as experimental arthritis and encephalomyelitis. A common feature of the local pathology of these diseases is an extensive infiltration of activated macrophages (M). Different functional activation states can be induced in M during innate immune activation, and it is this differential activation that might be important in susceptibility/resistance to induction or perpetuation of autoimmunity. In this study, we present an extensive, comparative analysis of the activation phenotypes of M derived from autoimmune-susceptible and autoimmune-resistant rat strains to describe a cellular phenotype that defines the disease phenotype. We included investigation of receptor function, intracellular signaling pathways, cytokines, and other soluble mediators released after activation of cells using a panel of stimuli embracing many activation routes. We report that activation of M from the autoimmune-susceptible strain was associated with alternative activation indicated by induction of arginase activity, a lower production of classical proinflammatory mediators, and a high production of interleukin (IL)-23, and M from the autoimmune-resistant strains were associated with a higher production of proinflammatory mediators, a classical activation phenotype, and preferential induction of IL-12. These M phenotypes thus reflect disparate, genetic cellular programs that define autoimmune susceptibility.

Key Words: cytokine • macrophage activation • autoimmunity

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