Ectopic expression of the murine chemokines CCL21a and CCL21b induces the formation of lymph node-like structures in pancreas, but not skin, of transgenic mice.
The CC chemokine CCL21 is a potent chemoattractant for lymphocytes and dendritic cells in vitro. In the murine genome there are multiple copies of CCL21 encoding two CCL21 proteins that differ from each other by one amino acid at position 65 (either a serine or leucine residue). In this report, we examine the expression pattern and biological activities of both forms of CCL21. We found that although both serine and leucine forms are expressed in most tissues examined, the former was the predominant form in lymphoid organs while the latter was predominantly expressed in nonlymphoid organs. When expressed in transgenic pancreas, both forms of CCL21 were capable of inducing the formation of lymph node-like structures composed primarily of T and B cells and a few dendritic cells. Induction of lymph node-like structures by these CCL21 proteins, however, could not be reproduced in every tissue. For instance, no lymphocyte recruitment or accumulation was observed when CCL21 was overexpressed in the skin. We conclude that both forms of CCL21 protein are biologically equivalent in promoting lymphocyte recruitment to the pancreas, and that their ability to induce the formation of lymph node-like structures is dependent on the tissues in which they are expressed.
Chen
Shu-Cheng
SC
Department of Immunology, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Vassileva
Galya
G
Kinsley
David
D
Holzmann
Sandra
S
Manfra
Denise
D
Wiekowski
Maria T
MT
Romani
Nikolaus
N
Lira
Sergio A
SA
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D002828:Choristoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008206:Lymphatic Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic / Q000276:immunology*; D009924:Organ Culture Techniques; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D010179:Pancreas; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D012867:Skin / Q000166:cytology / Q000378:metabolism; D019076:Transgenes / Q000276:immunology
C515479:Ccl21c protein, mouse; D054421:Chemokine CCL21; D019742:Chemokines, CC; D020033:Protein Isoforms