The class 6 semaphorin SEMA6A is induced by interferon-gamma and defines an activation status of langerhans cells observed in pathological situations.
Originally implicated in axon guidance, semaphorins represent a large family of molecules that are now known to be expressed in the immune system. Among different semaphorins tested by reverse transcriptase-polymerase chain reaction in human immune cells, the expression of class 6 transmembrane semaphorin SEMA6A was restricted to dendritic cells (DCs). Using in-house generated monoclonal antibodies, SEMA6A expression appeared further restricted to Langerhans cells (LCs). In vivo, SEMA6A mRNA was expressed in freshly isolated skin LCs but SEMA6A protein was not detectable on normal skin and tonsillar epithelium. Of interest, SEMA6A protein was strongly expressed on skin and bone LCs and on LCs in draining lymph nodes from patients with LC histiocytosis or dermatopathic lymphadenitis, respectively, representing two inflammatory conditions in which LCs display an immature DC-LAMP(low), CD83(low), and CCR7+ phenotype. SEMA6A expression was low in resting LCs generated in vitro and was enhanced by interferon (IFN)-gamma but not by interleukin-4, interleukin-10, IFN-alpha/beta, or lipopolysaccharide. Most IFN-gamma-induced SEMA6A-positive cells remained immature with low CD83 and DC-LAMP/CD208 expression, but they expressed CCR7 and responded to macrophage inflammatory protein-3beta (MIP-3beta/CCL19). The expression of SEMA6A, for which the ligand and function remain unknown, may therefore identify an alternative IFN-gamma-dependent activation status of LCs in vivo.
Gautier
Gregory
G
Laboratory for Immunological Research, Dardilly, France.
de Saint-Vis
Blandine
B
Sénéchal
Brigitte
B
Pin
Jean-Jacques
JJ
Bates
Elizabeth E M
EE
Caux
Christophe
C
Geissmann
Frédéric
F
Garrone
Pierre
P
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001842:Bone and Bones / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism; D002465:Cell Movement; D054415:Chemokine CCL19; D019742:Chemokines, CC / Q000494:pharmacology; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015614:Histiocytosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007136:Immunoglobulins; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D016753:Interleukin-10 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000473:pathology; D008199:Lymphadenitis / Q000378:metabolism* / Q000473:pathology; D019402:Macrophage Inflammatory Proteins; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D014066:Palatine Tonsil / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D039961:Semaphorins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000097802:CD83 Antigen
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D054415:Chemokine CCL19; D019742:Chemokines, CC; D007136:Immunoglobulins; D016898:Interferon-alpha; D016899:Interferon-beta; D007371:Interferon-gamma; D016753:Interleukin-10; D015847:Interleukin-4; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D039961:Semaphorins; D000097802:CD83 Antigen; C515460:CCL19 protein, human; C515370:CCR7 protein, human; C515461:Ccl19 protein, mouse; C515371:Ccr7 protein, mouse; C504201:SEMA6A protein, human