Lymphoid tissue homing chemokines are expressed in chronic inflammation.
Secondary lymphoid tissue chemokine (SLC) and B lymphocyte chemoattractant (BLC) are homing chemokines that have been implicated in the trafficking of lymphocytes and dendritic cells in lymphoid organs. Lymphotoxin-alpha (LTalpha), a cytokine crucial for development of lymphoid organs, is important for expression of SLC and BLC in secondary lymphoid organs during development. Here we report that transgenic expression of LTalpha induces inflammation and ectopic expression of SLC and BLC in the adult animal. LTbeta was not necessary for induction of BLC and SLC in inflamed tissues, whereas, in contrast, tumor necrosis factor receptor-1 was found to be important for the LTalpha-mediated induction of these chemokines. The ectopic expression of LTalpha is associated with a chronic inflammation that closely resembles organized lymphoid tissue and this lymphoid neogenesis can also be seen in several chronic inflammatory diseases, including in the pancreas of the prediabetic nonobese diabetic (NOD) mouse. Expression of SLC was also observed in the pancreas of prediabetic NOD mice. This study implicates BLC and SLC in chronic inflammation and presents further evidence that LTalpha orchestrates lymphoid organogenesis both during development and in inflammatory processes.
Hjelmström
P
P
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520-8034, USA.
Fjell
J
J
Nakagawa
T
T
Sacca
R
R
Cuff
C A
CA
Ruddle
N H
NH
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D054421:Chemokine CCL21; D054382:Chemokine CXCL13; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D002908:Chronic Disease; D005260:Female; D007249:Inflammation / Q000378:metabolism*; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000502:physiology; D053308:Lymphotoxin-beta; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D016688:Mice, Inbred NOD / Q000235:genetics; D008822:Mice, Transgenic / Q000235:genetics; D010179:Pancreas / Q000378:metabolism; D010195:Pancreatitis / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D047888:Receptors, Tumor Necrosis Factor, Type I
D015703:Antigens, CD; C515479:Ccl21c protein, mouse; D054421:Chemokine CCL21; D054382:Chemokine CXCL13; D019742:Chemokines, CC; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; C505887:Ltb protein, mouse; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I