Disease relevance of Ccl21b

• TCA-4 protein was not detected on the luminal surface of PLN HEVs in plt/plt mice, which have a congenital defect in T cell homing to PLNs [1].
• Similar findings are seen when mice are treated with pertussis toxin, which blocks chemokine signaling in vivo. plt/plt mice had increased susceptibility to L. donovani infection compared with wild-type mice, as determined by spleen and liver parasite burden [2].

High impact information on Ccl21b

• Focus formation in rat fibroblasts exposed to a tumour promoter after transfer of polyoma plt and myc oncogenes [3].
• Both parameters were comparably reduced for WT T lymphocytes migrating in T cell areas of plt/plt mice lacking CCR7 ligands [4].
• Homing experiments in paucity of lymph node T cells (plt/plt) mice, which do not express CCR7 ligands in secondary lymphoid organs, revealed that T(CM) migrate to PLNs at approximately 20% of wild-type (WT) levels, whereas homing of naive T cells was reduced by 95% [5].
• Sticking of T(CM) in plt/plt HEVs was pertussis toxin sensitive and was blocked by anti-CXCL12 (SDF-1alpha) [5].
• Accordingly, a large fraction of endogenous CD8(+) T cells in plt/plt PLNs displayed a T(CM) phenotype [5].

Biological context of Ccl21b

• CXCL9-antagonism extended graft survival significantly only in plt mice, likely due, in part, to retention of alloactivated T cells in secondary lymphoid tissue/reduction of graft-infiltrating T cells [6].
• Previously, we have shown a mutant mouse DDD/1 with T-cell-specific homing defect that is regulated by an autosomal recessive gene, plt (paucity of lymph node T cells), and seems to be caused by lymph node (LN) stromal cells [7].
• Linkage mapping by simple-sequence length polymorphism of genomic DNA from 190 backcross progenies produced by intercrossing with MSM/Ms, linked plt most closely with D4Mit237, and localized at 24.7 cM from cetromere on chromosome 4 [7].
• Four weeks after cessation of inhalation, airway inflammation and hyperresponsiveness in plt mice were greater than in BALB/c mice [8].
• This was associated with upregulation of ALPP and subsequent activation of the Akt signaling pathway [9].

Anatomical context of Ccl21b

• The spontaneous mutant mouse strain, plt/plt, lacks the secondary lymphoid organ chemokine (SLC)-ser gene and has disrupted trafficking of T cells and dendritic cells (DCs) to lymphoid tissues [10].
• In contrast, the NALT of plt/plt mice is nearly normal, with follicular dendritic cells, BP3(+) stromal cells, ERTR7(+) lymphoreticular cells, and peripheral node addressin(+) HEVs [11].
• Paucity of lymph node T-cells (plt/plt) mice lack CCL21-serine (ser) and CCL19 expression [6].
• Donor DC trafficking to secondary lymphoid tissue was markedly reduced in plt heart but not skin allograft recipients [6].
• Intravital microscopy of plt/plt subiliac lymph nodes showed that T(CM) rolled and firmly adhered (sticking) in high endothelial venules (HEVs), whereas naive T cells were incapable of sticking [5].

Associations of Ccl21b with chemical compounds

• In this study we demonstrate that FTY720 rescues the homing defect in both CCR7(-/-) mice and plt mice [12].
• Although airway inflammation and response to acetylcholine were significantly reduced compared with BALB/c mice, significant eosinophilic inflammation and hyperresponsiveness were also observed in plt mice after 2 weeks of inhalation [8].
• Studies on the effect of actinomycin D or cycloheximide treatment indicated that the vitamin may enhance de novo synthesis of ALP [13].
• Moreover, the anti-estrogen tamoxifen eliminated the stimulation of MC3T3-E1 cells on the proliferation, ALP activity and collagen synthesis by soy extract, indicating that the main action of the soy extract on osteoblastic MC3T3-E1 cells is similar to that of estrogen effects [14].
• Identical enzyme labels (alkaline phosphatase, ALP) and substrates (p-aminophenyl phosphate, PAPP) are used for all analytes [15].

Regulatory relationships of Ccl21b

• Anti-CXCL9/Mig was administered for 2 weeks post-transplant to determine whether impairment of activated T-cell migration could further prolong cardiac allograft survival in plt recipients [6].

Other interactions of Ccl21b

• We also show that the NALT of Cxcl13(-/-) and plt/plt mice exhibits some, but not all, of the structural and functional defects observed in the NALT of Ltalpha(-/-) mice [11].
• In contrast, accumulation of mRNA for IL-10 was elevated in plt/plt mice [2].

Analytical, diagnostic and therapeutic context of Ccl21b

• Accordingly, T cells from plt heart transplant recipients demonstrated poor anti-donor responses in ex vivo MLR, compared to wt heart or wt and plt skin recipients [6].
• The numbers of ALP-positive cells in the mouse fibroblastic cell line C3H10T1/2 and the mouse osteoblastic cell line MC3T3-E1 were increased by co-culture with chicken fibroblasts transfected with chicken Shh cDNA encoding amino-terminal peptide (Shh-N) [16].
• Controls were untreated (NT) or received only the vaccination protocol (ALP) [17].

References