Expression of rat I-TAC/CXCL11/SCYA11 during central nervous system inflammation: comparison with other CXCR3 ligands.
The chemokines are a large gene superfamily with critical roles in development and immunity. The chemokine receptor CXCR3 appears to play a major role in the trafficking of activated Th1 lymphocytes. There are at least three major ligands for CXCR3: mig/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11, and of these three ligands, CXCL11 is the least well-characterized. In this study, we have cloned a rat ortholog of CXCL11, evaluated its function, and examined its expression in the Th-1-mediated disease, experimental autoimmune encephalomyelitis (EAE) in the rat. Based on its predicted primary amino-acid sequence, rat I-TAC/CXCL11 was synthesized and shown to induce chemotaxis of activated rat T lymphocytes in vitro and the in vivo migration of T lymphocytes when injected into the skin. I-TAC/CXCL11 expression, as determined by RT-PCR, increased in lymph node and spinal cord tissue collected from rats in which EAE had been actively induced, and in spinal cord tissue from rats in which EAE had been passively induced. The kinetics of expression were similar to that of CXCR3 and IP-10/CXCL10, although expression of both CXCR3 and IP-10/CXCL10 was more intense than that of I-TAC/CXCL11 and increased more rapidly in both lymph nodes and the spinal cord. Only minor levels of expression of the related chemokine mig/CXCL9 were observed. Immunohistochemistry revealed that the major cellular source of I-TAC/CXCL11 in the central nervous system (CNS) during EAE is likely to be the astrocyte. Together, these data indicate that I-TAC/CXCL11 is expressed in the CNS during the clinical phase of EAE. However, the observation that I-TAC/CXCL11 is expressed after receptor expression is detected suggests that it is not essential for the initial migration of CXCR3-bearing cells into the CNS.
School of Molecular & Biomedical Science, Adelaide University, Adelaide, South Australia, Australia. shaun.mccoll@adelaide.edu.au
Shaun R
SR
McColl
Surendran
S
Mahalingam
Maria
M
Staykova
Laurie A
LA
Tylaska
Katherine E
KE
Fisher
Christine A
CA
Strick
Ronald P
RP
Gladue
Kuldeep S
KS
Neote
David O
DO
Willenborg
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D054413:Chemokine CCL11; D054371:Chemokine CXCL11; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008024:Ligands; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology
C515456:CCL11 protein, human; C515202:CXCL11 protein, human; C515187:CXCR3 protein, human; C515458:Ccl11 protein, rat; D054413:Chemokine CCL11; D054371:Chemokine CXCL11; D019742:Chemokines, CC; D019743:Chemokines, CXC; C515205:Cxcl11 protein, rat; C515189:Cxcr3 protein, rat; D008024:Ligands; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine