IP-10 and type 1 diabetes: a question of time and location.
Chemokines are key signal molecules that attract cells of the host immune system to the site of a potential threat. Virus infections usually induce a massive chemokine and cytokine burst and therefore recruit a large plethora of leukocytes to the site of infection with the goal to restrict and abrogate viral spread. The down side of this massive excitation of the human defense system is non-specific activation of potentially self-reactive lymphocytes. Coupled with an antigen-specific event, for example molecular mimicry between host commponents and viral proteins, autoimmunity might be the consequence in susceptible individuals. However, activated immune components with autoaggressive potential must find their target and must remain in one site sufficiently long in order to cause chronic tissue damage. In this review we will focus on the influence of the chemokine IP-10 (CXCL10) on the trafficking of autoaggressive cells during the immunopathogenesis of type 1 diabetes (T1D) and explain why IP-10 can have a dual effect on T1D depending on time and location of expression.
Christen
Urs
U
Department of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA, USA. christen@liai.org
Von Herrath
Matthias G
MG
D000818:Animals; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005822:Genetic Vectors; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; D006023:Glycoproteins; D009698:Nucleoproteins; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D014764:Viral Proteins