CD44 involvement in autoimmune inflammations: the lesson to be learned from CD44-targeting by antibody or from knockout mice.
CD44 is a multistructural and multifunctional glycoprotein, the diversity of which is generated by alternative splicing. In this communication we review some aspects related to CD44 structure and function in experimental autoimmune inflammation, focusing on research performed in our own laboratory. We have found that CD44 targeting by antibody, passively injected into DBA/1 mice with collagen-induced arthritis (CIA) and NOD mice with type I diabetes or actively generated by CD44 cDNA vaccination of SJL/j mice with autoimmune encephalomyelitis, markedly reduced the pathological manifestations of these diseases by attenuating cell migration of the inflammatory cells and/or by their apoptotic killing. However, genetic deletion of CD44 by knockout technology enhanced the development of CIA because of molecular redundancy mediated by RHAMM (a receptor of hyaluronan-mediated motility). The mechanisms that stand behind these findings are discussed.
Naor
David
D
The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel. naord@md.huji.ac.il
Nedvetzki
Shlomo
S
Walmsley
Marita
M
Yayon
Avner
A
Turley
Eva A
EA
Golan
Ira
I
Caspi
Dan
D
Sebban
Lora Eshkar
LE
Zick
Yehiel
Y
Garin
Tali
T
Karussis
Dimitrios
D
Assayag-Asherie
Nathalie
N
Raz
Itamar
I
Weiss
Lola
L
Slavin
Shimon
S
Golan
Itshak
I
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D004195:Disease Models, Animal; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology* / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout
D000906:Antibodies; D018960:Hyaluronan Receptors; D003094:Collagen