title: Endogenous galectin-1 exerts tonic inhibition on experimental arthritis.
abstract: Little is known about the role(s) of endogenous galectin-1 (Gal-1) in arthritis. In this study we queried whether antiarthritic functions for this effector of endogenous anti-inflammation could be unveiled by studying collagen-induced arthritis in Gal-1(-/-) mice. Gal-1(-/-) and C57BL/6J [wild-type (WT)] mice received an immunization of chicken type II collagen (CII) in CFA followed by a booster on day 21, which consisted of CII in IFA. Animals were monitored for signs of arthritis from day 14 onward. Clinical and histological signs of arthritis were recorded, and humoral and cellular immune responses against CII were analyzed. A distinct disease penetrance was apparent, with ~ 70% of Gal-1(-/-) mice developing arthritis compared with ~ 50% in WT animals. Gal-1(-/-) mice also exhibited an accelerated disease onset and more severe arthritis characterized by significantly elevated clinical scores. Postmortem analyses (day 42) revealed higher levels of IgG1 and IgG2b anti-CII Ig isotypes in the serum of Gal-1 null animals compared with WT. Finally, T cell responses following ex vivo stimulation with CII revealed a greater degree of proliferation in T cells of Gal-1(-/-) mice compared with WT, which was associated with increased production of IL-17 and IL-22. These data suggest the novel idea that endogenous Gal-1 is an inhibitory factor in the development of arthritis affecting disease severity. We have also highlighted the importance of endogenous Gal-1 in regulating T cell reactivity during experimental arthritis.
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Asif J
authors.initials: AJ
authors.lastname: Iqbal
authors.forename: Dianne
authors.initials: D
authors.lastname: Cooper
authors.forename: Alexander
authors.initials: A
authors.lastname: Vugler
authors.forename: Beatrice R
authors.initials: BR
authors.lastname: Gittens
authors.forename: Adrian
authors.initials: A
authors.lastname: Moore
authors.forename: Mauro
authors.initials: M
authors.lastname: Perretti
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000175:diagnosis* / Q000453:epidemiology / Q000517:prevention & control*; D005260:Female; D037483:Galectin 1 / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology; D015994:Incidence; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D012720:Severity of Illness Index
chemical_list: D037483:Galectin 1