Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Federico ParoniEmail author
  • Kathrin Maedler
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_239


Historical Background

Chemokines/chemoattractant cytokines are small proteins with a mass of 8–10 kDa. Cytokines and chemokines are effector molecules that play a pivotal role in orchestrating both the innate and acquired immune responses. Additionally, they are involved in cell differentiation, division, and repair. The chemokine’s nomenclature has been established in the early 1990s at the International Symposium on Chemotactic Cytokines in Baden (Lindley et al. 1993) on the base of the N-term conserved cysteine motif. Chemokines are classified into four families: C, CC, CXC, CX3C, where X represent any amino acid residue. CXCL10, also called interferon-γ-inducible protein 10 (IP-10), has been initially identified as a chemokine induced by interferon-γ and secreted by a variety of tissues, for example, endothelial cells, monocytes, fibroblasts, and keratinocytes (Luster and...

This is a preview of subscription content, log in to check access.


  1. Cardozo AK, Proost P, et al. IL-1beta and IFN-gamma induce the expression of diverse chemokines and IL-15 in human and rat pancreatic islet cells, and in islets from pre-diabetic NOD mice. Diabetologia. 2003;46(2):255–66.PubMedCrossRefGoogle Scholar
  2. Christen U, Von Herrath MG. IP-10 and type 1 diabetes: a question of time and location. Autoimmunity. 2004;37(5):273–82.PubMedCrossRefGoogle Scholar
  3. Christen U, McGavern DB, et al. Among CXCR3 chemokines, IFN-gamma-inducible protein of 10 kDa (CXC chemokine ligand (CXCL) 10) but not monokine induced by IFN-gamma (CXCL9) imprints a pattern for the subsequent development of autoimmune disease. J Immunol. 2003;171(12):6838–45.PubMedCrossRefGoogle Scholar
  4. Delovitch TL, Singh B. The nonobese diabetic mouse as a model of autoimmune diabetes: immune dysregulation gets the NOD. Immunity. 1997;7(6):727–38.PubMedCrossRefGoogle Scholar
  5. Donath MY, Halban PA. Decreased beta-cell mass in diabetes: significance, mechanisms and therapeutic implications. Diabetologia. 2004;47:581–9.PubMedCrossRefGoogle Scholar
  6. Ehses JA, Perren A, et al. Increased number of islet-associated macrophages in type 2 diabetes. Diabetes. 2007;56(9):2356–70.PubMedCrossRefGoogle Scholar
  7. Frigerio S, Junt T, et al. Beta cells are responsible for CXCR3-mediated T-cell infiltration in insulitis. Nat Med. 2002;8(12):1414–20.PubMedCrossRefGoogle Scholar
  8. Hanaoka R, Kasama T, et al. A novel mechanism for the regulation of IFN-gamma inducible protein-10 expression in rheumatoid arthritis. Arthritis Res Ther. 2003;5(2):R74–81.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Herder C, Baumert J, et al. Chemokines as risk factors for type 2 diabetes: results from the MONICA/KORA Augsburg study, 1984–2002. Diabetologia. 2006;49(5):921–9.PubMedCrossRefGoogle Scholar
  10. Herder C, Hauner H, et al. Constitutive and regulated expression and secretion of interferon-gamma-inducible protein 10 (IP-10/CXCL10) in human adipocytes. Int J Obes (Lond). 2007a;31(3):403–10.CrossRefGoogle Scholar
  11. Herder C, Schneitler S, et al. Low-grade inflammation, obesity, and insulin resistance in adolescents. J Clin Endocrinol Metab. 2007b;92(12):4569–74.PubMedCrossRefGoogle Scholar
  12. Li D, Zhu SW, et al. Expression of interferon inducible protein-10 in pancreas of mice. World J Gastroenterol. 2005;11(30):4750–2.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Lindley IJD, Westwick J, Kunkel SL. Nomenclature announcement: the chemokines. Immunol Today. 1993;14:24.Google Scholar
  14. Luster AD, Ravetch JV. Biochemical characterization of a gamma interferon-inducible cytokine (IP-10). J Exp Med. 1987;166(4):1084–97.PubMedCrossRefGoogle Scholar
  15. Morimoto J, Yoneyama H, et al. CXC chemokine ligand 10 neutralization suppresses the occurrence of diabetes in nonobese diabetic mice through enhanced beta cell proliferation without affecting insulitis. J Immunol. 2004;173(11):7017–24.PubMedCrossRefGoogle Scholar
  16. Nicoletti F, Conget I, et al. Serum concentrations of the interferon-gamma-inducible chemokine IP-10/CXCL10 are augmented in both newly diagnosed type I diabetes mellitus patients and subjects at risk of developing the disease. Diabetologia. 2002;45(8):1107–10.PubMedCrossRefGoogle Scholar
  17. Paroni F, Domsgen E, et al. CXCL10- a path to beta-cell death. Islets. 2009;1(3):256–9.PubMedCrossRefGoogle Scholar
  18. Rhode A, Pauza ME, et al. Islet-specific expression of CXCL10 causes spontaneous islet infiltration and accelerates diabetes development. J Immunol. 2005;175(6):3516–24.PubMedCrossRefGoogle Scholar
  19. Roep BO, Kleijwegt FS, et al. Islet inflammation and CXCL10 in recent-onset type 1 diabetes. Clin Exp Immunol. 2010;159(3):338–43.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Rotondi M, Lazzeri E, et al. Role for interferon-gamma inducible chemokines in endocrine autoimmunity: an expanding field. J Endocrinol Invest. 2003a;26(2):177–80.PubMedCrossRefGoogle Scholar
  21. Rotondi M, Romagnani P, et al. to: Nicoletti F, Conget L, Di Mauro M et al. (2002) Serum concentrations of the interferon-alpha-inducible chemokine IP-10/CXCL10 are augmented in both newly-diagnosed Type I diabetes mellitus patients and subjects at risk of developing the disease. Diabetologia 45:1107–1110. Diabetologia. 2003b;46(7):1020–1.Google Scholar
  22. Rotondi M, Chiovato L, et al. Role of chemokines in endocrine autoimmune diseases. Endocr Rev. 2007;28(5):492–520.PubMedCrossRefGoogle Scholar
  23. Schulthess FT, Paroni F, et al. CXCL10 impairs beta cell function and viability in diabetes through TLR4 signaling. Cell Metab. 2009;9(2):125–39.PubMedCrossRefGoogle Scholar
  24. Shimabukuro M, Zhou YT, et al. Fatty acid-induced beta cell apoptosis: a link between obesity and diabetes. Proc Natl Acad Sci U S A. 1998;95(5):2498–502.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Shimada A, Morimoto J, et al. Elevated serum IP-10 levels observed in type 1 diabetes. Diabetes Care. 2001;24(3):510–5.PubMedCrossRefGoogle Scholar
  26. Strieter RM, Polverini PJ, et al. The functional role of the ELR motif in CXC chemokine-mediated angiogenesis. J Biol Chem. 1995;270(45):27348–57.PubMedCrossRefGoogle Scholar
  27. Xu H, Nakayama K, et al. Elevated plasma concentration of IP-10 in patients with type 2 diabetes mellitus. Nihon Jinzo Gakkai Shi. 2005;47(5):524–30.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Center for Biomolecular InteractionsUniversity of BremenBremenGermany