title: CD11b regulates the Treg/Th17 balance in murine arthritis via IL-6.
abstract: Th17 cells are often associated with autoimmunity and been shown to be increased in CD11b-/-mice. Here, we examined the role of CD11b in murine collagen-induced arthritis (CIA). C57BL/6 and CD11b-/-resistant mice were immunized with type II collagen. CD11b-/-mice developed arthritis with early onset, high incidence, and sustained severity compared with C57BL/6 mice. We observed a marked leukocyte infiltration, and histological examinations of the arthritic paws from CD11b-/-mice revealed that the cartilage was destroyed in association with strong lymphocytic infiltration. The CD11b deficiency led to enhanced Th17-cell differentiation. CD11b-/-dendritic cells (DCs) induced much stronger IL-6 production and hence Th17-cell differentiation than wild-type DCs. Treatment of CD11b-/-mice after establishment of the Treg/Th17 balance with an anti-IL-6 receptor mAb significantly suppressed the induction of Th17 cells and reduced arthritis severity. Finally, the severe phenotype of arthritis in CD11b-/-mice was rescued by adoptive transfer of CD11b+DCs. Taken together, our results indicate that the resistance to CIA in C57BL/6 mice is regulated by CD11b via suppression of IL-6 production leading to reduced Th17-cell differentiation. Therefore, CD11b may represent a susceptibility factor for autoimmunity and could be a target for future therapy.
authors.affiliation: Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
authors.forename: Mathias
authors.initials: M
authors.lastname: Stevanin
authors.affiliation: DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Epalinges, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Busso
authors.affiliation: DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Epalinges, Switzerland.
authors.forename: Véronique
authors.initials: V
authors.lastname: Chobaz
authors.affiliation: Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
authors.forename: Matteo
authors.initials: M
authors.lastname: Pigni
authors.affiliation: Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
authors.forename: Sahar
authors.initials: S
authors.lastname: Ghassem-Zadeh
authors.affiliation: Center for Vascular and Inflammatory Diseases, Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
authors.forename: Hans
authors.initials: H
authors.lastname: Acha-Orbea
authors.affiliation: Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
authors.forename: Driss
authors.initials: D
authors.lastname: Ehirchiou
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000276:immunology*; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism*; D002356:Cartilage / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D024043:Collagen Type II / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D015850:Interleukin-6 / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019947:Receptors, Interleukin-6 / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D039481:CD11b Antigen; D024043:Collagen Type II; D015850:Interleukin-6; D019947:Receptors, Interleukin-6
keywords: Arthritis; Autoimmunity; CD11b integrin; Dendritic cells; Th17