Neuronal repellent Slit2 inhibits dendritic cell migration and the development of immune responses.
One of the essential functions of dendritic cells is to take up Ags in peripheral tissues and migrate into secondary lymphoid organs to present Ags to lymphocytes for the induction of immune responses. Although many studies have demonstrated that the migration of dendritic cells is closely associated with the development of immune responses, little is known about factors that inhibit dendritic cell migration and control the extent of immune responses to Ag stimulation. We show that Slit2, a neuronal repellent factor, is up-regulated in the skin by allergen sensitization and down-regulates the migration of Langerhans cells. The effect is mediated by direct interaction of Slit2 with cells that express a Slit-specific receptor, Robo1. Slit2-mediated inhibition of Langerhans cell migration results in suppression of contact hypersensitivity responses. These findings provide insights into a novel mechanism by which Slit2 functions as an anti-inflammatory factor for the initiation of immune responses.
Guan
Hongbing
H
Department of Dermatology, University of Alabama, Birmingham, AL 35294, USA.
Zu
Guorui
G
Xie
Yi
Y
Tang
Hao
H
Johnson
Martin
M
Xu
Xiaochun
X
Kevil
Christophe
C
Xiong
Wen-Cheng
WC
Elmets
Craig
C
Rao
Yi
Y
Wu
Jane Y
JY
Xu
Hui
H
D000818:Animals; D002450:Cell Communication / Q000276:immunology; D002460:Cell Line; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology / Q000517:prevention & control; D004139:Dinitrofluorobenzene / Q000008:administration & dosage; D005260:Female; D006241:Haptens / Q000008:administration & dosage; D006801:Humans; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000378:metabolism; D007279:Injections, Subcutaneous; D036341:Intercellular Signaling Peptides and Proteins; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D009924:Organ Culture Techniques; D010081:Oxazolone / Q000008:administration & dosage; D011971:Receptors, Immunologic / Q000502:physiology; D012867:Skin / Q000378:metabolism; D012995:Solubility; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
D004139:Dinitrofluorobenzene; D006241:Haptens; D007166:Immunosuppressive Agents; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D010081:Oxazolone; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein