title: Signaling lymphocyte activation molecule regulates development of colitis in mice.
abstract: OBJECTIVE
  Signaling lymphocyte activation molecule (Slamf)1 is a co-stimulatory receptor on T cells and regulates cytokine production by macrophages and dendritic cells. Slamf1 regulates microbicidal mechanisms in macrophages, therefore we investigated whether the receptor affects development of colitis in mice.
  
  
  METHODS
  We transferred CD45RB(hi) CD4(+) T cells into Rag(-/-) or Slamf1(-/-)Rag(-/-) mice to induce colitis. We also induced colitis by injecting mice with an antibody that activates CD40. We determined the severity of enterocolitis based on disease activity index, histology scores, and levels of cytokine production, and assessed the effects of antibodies against Slamf1 on colitis induction. We quantified migration of monocytes and macrophage to inflamed tissues upon induction of colitis or thioglycollate-induced peritonitis and in response to tumor necrosis factor-α in an air-pouch model of leukocyte migration.
  
  
  RESULTS
  Colitis was reduced in Slamf1(-/-)Rag(-/-) mice, compared with Rag(-/-) mice, after transfer of CD45RB(hi) CD4(+) T cells or administration of the CD40 agonist. The numbers of monocytes and macrophages were reduced in inflamed tissues of Slamf1(-/-)Rag(-/-) mice, compared with Rag(-/-) mice, after induction of colitis and other inflammatory disorders. An antibody that inhibited Slamf1 reduced the level of enterocolitis in Rag(-/-) mice.
  
  
  CONCLUSIONS
  Slamf1 contributes to the development of colitis in mice. It appears to indirectly regulate the appearance of monocytes and macrophages in inflamed intestinal tissues. Antibodies that inhibit Slamf1 reduce colitis in mice, so human SLAMF1 might be a therapeutic target for inflammatory bowel disease.
authors.affiliation: Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Boaz
authors.initials: B
authors.lastname: van Driel
authors.forename: Gongxian
authors.initials: G
authors.lastname: Liao
authors.forename: Xavier
authors.initials: X
authors.lastname: Romero
authors.forename: Michael S
authors.initials: MS
authors.lastname: O'Keeffe
authors.forename: Guoxing
authors.initials: G
authors.lastname: Wang
authors.forename: William A
authors.initials: WA
authors.lastname: Faubion
authors.forename: Scott B
authors.initials: SB
authors.lastname: Berger
authors.forename: Erica M
authors.initials: EM
authors.lastname: Magelky
authors.forename: Monika
authors.initials: M
authors.lastname: Manocha
authors.forename: Veronica
authors.initials: V
authors.lastname: Azcutia
authors.forename: Matthew
authors.initials: M
authors.lastname: Grisham
authors.forename: Francis W
authors.initials: FW
authors.lastname: Luscinskas
authors.forename: Emiko
authors.initials: E
authors.lastname: Mizoguchi
authors.forename: Rene
authors.initials: R
authors.lastname: de Waal Malefyt
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Reinecker
authors.forename: Atul K
authors.initials: AK
authors.lastname: Bhan
authors.forename: Ninghai
authors.initials: N
authors.lastname: Wang
authors.forename: Cox
authors.initials: C
authors.lastname: Terhorst
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D019013:CD40 Antigens / Q000009:adverse effects; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000097:blood; D054410:Chemokine CCL7 / Q000097:blood; D003092:Colitis / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D004195:Disease Models, Animal; D007422:Intestines / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
chemical_list: D015703:Antigens, CD; D019013:CD40 Antigens; C491768:Ccl2 protein, mouse; C515451:Ccl7 protein, mouse; D018932:Chemokine CCL2; D054410:Chemokine CCL7; D011956:Receptors, Cell Surface; C000604059:SLAMF1 protein, human; C000604062:Slamf1 protein, mouse; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1