Research Report 2010 - MDC

Tumor ImmunologyMartin LippStructure of the GroupGroup LeaderDr. Martin LippScientistsDr. Uta E. HöpkenDr. Gerd MüllerDr. Hossein PanjidehDr. med. Tobias SchulzeDr. Jörg Rossbacher*Dr. Peter Rahn (FACS Operator)Differentiation and Growth Controlin Lymphocyte Development andImmunopathogenesisChemokines are essential regulators of lymphocyte migration throughout the body. Thechemokine system controls lymphocyte recirculation in immune system homeostasis aswell as the activation-dependent and tissue-selective trafficking of lymphocytes and dendriticcells during immune responses. In addition, chemokines are critical factors for the developmentand organization of secondary lymphoid organs. Our main focus is the role of homeostaticchemokine receptors like CXCR5 and CCR7 in lymphoid organ development, systemic immuneresponses, and chronic inflammatory diseases. In addition, we are interested in the immunemodulatory and growth-inducing functions of chemokine receptors encoded by humanherpesviruses, and the function of sphingophospholipid receptors in the immune system.CCR7 mediates homeostatic lymphocyterecirculation and mucosal immunityThe homeostatic chemokine receptor CCR7 controls notonly lymphocyte trafficking to and within secondarylymphoid organs, but also homeostatic migration of Tand B lymphocytes through non-lymphoid peripheraltissues. CCR7 deficiency results in a massive accumulationof T- and B-lymphocytes in the peritoneal cavity.Mechanistically, the increase in the number of peritoneallymphocytes is caused by an impaired egress ofCCR7-deficient lymphocytes from body cavities. Mostinterestingly, a disturbed peripheral recirculation oflymphocytes also resulted in the development ofectopic lymphoid-like follicles and age-dependenthistopathological changes in the gastrointestinal tractof CCR7-deficient mice. Since the formation of ectopicfollicles precedes the development of epithelial histomorphologicalchanges, we suggest that crosstalkbetween lymphoid aggregates and their adjacentepithelial tissue might contribute to the developmentof hypertrophic gastropathy. The underlying molecularmechanisms have been addressed by performingexpression profiling of differentially expressed genesbetween wild-type epithelial tissue and CCR7 -/- epithelialtissue or mucosal lymphoid aggregates. Severaltranscription factors and signaling molecules wereselected on basis of the microarray data and are furthercharacterized as potential mediators involved in thiscellular crosstalk.CXCR5-dependent autoantigen-driven lymphoidneo-genesis in a chronic murine model ofrheumatoid arthritisRheumatoid arthritis (RA) is a common autoimmunedisease with unknown etiology that affects around 1%of the population. In RA, chronic inflammation of the116 Cancer Research