Brian Wu1,2,3, Akihiro Nakamura4,5,6,7. 1. Schroeder Arthritis Institute, University Health Network, 60 Leonard Avenue, Toronto, ON, M5T 0S8, Canada. 2. Krembil Research Institute, University Health Network, Toronto, ON, Canada. 3. Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada. 4. Schroeder Arthritis Institute, University Health Network, 60 Leonard Avenue, Toronto, ON, M5T 0S8, Canada. Akihiro.Nakamura@uhnresearch.ca. 5. Krembil Research Institute, University Health Network, Toronto, ON, Canada. Akihiro.Nakamura@uhnresearch.ca. 6. Division of Rheumatology, Toronto Western Hospital, University Health Network, Toronto, ON, Canada. Akihiro.Nakamura@uhnresearch.ca. 7. Institute of Medical Science, Temerty Faculty of Medicine of Medicine, University of Toronto, Toronto, ON, Canada. Akihiro.Nakamura@uhnresearch.ca.
Abstract
PURPOSE OF REVIEW: Pathological roles of macrophage migration inhibitory factor (MIF) have recently been demonstrated in spondyloarthritis (SpA) preclinical models, identifying MIF as a new treatment target for SpA. However, the specific contribution of MIF and therapeutic potential of MIF-targeted therapies to various tissue types affected by SpA are not well delineated. RECENT FINDINGS: MIF and its cognate receptor CD74 are extensively involved in the pathogenesis of SpA including inflammation in the spine, joint, eyes, skin, and gut. The majority of the current evidence has consistently shown that MIF drives the inflammation in these distinct anatomical sites. In preclinical models, genetic deletion or blockade of MIF reduces the severity of inflammation. Although MIF is generally an upstream cytokine which regulates downstream effector cytokines, MIF also intensifies type 3 immunity by promoting helper T 17 (Th17) plasticity. MIF- or CD74-targeted therapies have also reported to be well tolerated in clinical trials for other diseases. Recent findings suggest that MIF-CD74 axis is a new therapeutic target for SpA to improve various clinical features. Clinical trials for MIF- or CD74-targeted therapies for SpA patients are warranted.
PURPOSE OF REVIEW: Pathological roles of macrophage migration inhibitory factor (MIF) have recently been demonstrated in spondyloarthritis (SpA) preclinical models, identifying MIF as a new treatment target for SpA. However, the specific contribution of MIF and therapeutic potential of MIF-targeted therapies to various tissue types affected by SpA are not well delineated. RECENT FINDINGS: MIF and its cognate receptor CD74 are extensively involved in the pathogenesis of SpA including inflammation in the spine, joint, eyes, skin, and gut. The majority of the current evidence has consistently shown that MIF drives the inflammation in these distinct anatomical sites. In preclinical models, genetic deletion or blockade of MIF reduces the severity of inflammation. Although MIF is generally an upstream cytokine which regulates downstream effector cytokines, MIF also intensifies type 3 immunity by promoting helper T 17 (Th17) plasticity. MIF- or CD74-targeted therapies have also reported to be well tolerated in clinical trials for other diseases. Recent findings suggest that MIF-CD74 axis is a new therapeutic target for SpA to improve various clinical features. Clinical trials for MIF- or CD74-targeted therapies for SpA patients are warranted.
Authors: Alberta Y Hoi; Michael J Hickey; Pamela Hall; Jiro Yamana; Kim M O'Sullivan; Leilani L Santos; Will G James; A Richard Kitching; Eric F Morand Journal: J Immunol Date: 2006-10-15 Impact factor: 5.422
Authors: Antoine Sreih; Rana Ezzeddine; Lin Leng; Avery LaChance; Geraldine Yu; Yuka Mizue; Lakshman Subrahmanyan; Bernardo A Pons-Estel; Anna-Karin Abelson; Iva Gunnarsson; Elisabet Svenungsson; Joshua Cavett; Stuart Glenn; Lin Zhang; Ruth Montgomery; Andras Perl; Jane Salmon; Marta E Alarcón-Riquelme; John B Harley; Richard Bucala Journal: Arthritis Rheum Date: 2011-12