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Anti-Inflammatory Activity of Immunoglobulin G Resulting from Fc Sialylation
Yoshikatsu Kaneko,*Falk Nimmerjahn,*Jeffrey V. Ravetch
Immunoglobulin G (IgG) mediates pro- and anti-inflammatory activitiesthrough the engagement of its Fc fragment (Fc) with distinctFcg receptors (FcgRs). One class of Fc-FcgR interactions generatespro-inflammatory effects of immune complexes and cytotoxic antibodies.In contrast, therapeutic intravenous gamma globulin and itsFc fragments are anti-inflammatory. We show here that thesedistinct properties of the IgG Fc result from differential sialylationof the Fc core polysaccharide. IgG acquires anti-inflammatoryproperties upon Fc sialylation, which is reduced upon the inductionof an antigen-specific immune response. This differential sialylationmay provide a switch from innate anti-inflammatory activityin the steady state to generating adaptive pro-inflammatoryeffects upon antigenic challenge.
Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: ravetch{at}rockefeller.edu
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