Lymphoid tissue homing chemokines are expressed in chronic inflammation

Abstract

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.

Figure 1.

Northern blot analysis of BLC and SLC mRNA expression in RIPLT kidneys using DIG-labeled RNA probes. Wild-type (wt) spleen was used as a positive control tissue. Hybridization to a β-actin antisense probe was used to control for RNA loaded.

Figure 2.

In situ hybridization analysis of BLC and SLC mRNA expression in RIPLT kidneys using DIG-labeled RNA probes. Chemokine expression appears as dark gray to black staining in this figure. A, C, E, and G show BLC expression and B, D, F, and H show SLC expression in kidneys from RIPLT.wt (A and B), RIPLT. LTβ −/− (C and D), RIPLT. TNFR1 −/− (E and F), and wild-type control (G and H) mice. Kidneys from RIPLT.wt mice were hybridized with sense BLC (I) and sense SLC (J) probes as negative controls. Original magnification, ×125.

Figure 3.

SLC mRNA is expressed in the pancreas of RIPLT and NOD mice. In situ hybridization analysis of SLC mRNA expression in RIPLT (A) and NOD (B) pancreas using DIG-labeled RNA probes. SLC staining of infiltrating and connective tissue cells in the RIPLT.wt and NOD mice is seen in purple, and infiltrating cells are counterstained with methyl green. Original magnification, ×62.5 .