• Journal of Microbiology and Biotechnology
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• v.14 no.6
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• pp.1267-1274
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• 2004

Colostrum contains various kinds of cytokines including TGF-$\beta$ that has potent regulatory effects on cells of the immune system. We compared the levels of TGF-$\beta$1 and TGF-$\beta$2 in bovine and human colostrum. Based on the isoform-specific ELISA, bovine colostrum collected on day 1 post-delivery retained $53.71{\pm}29.55\;ng/ml$ of TGF-$\beta$1 and $40.41{\pm}21.78\;{\mu}g/ml$ of TGF-$\beta$2 (n=4), while in human, $381.45{\pm}158.24\;ng/ml$ of TGF-$\beta$1 and $41.47{\pm}9.63\;ng/ml$ of TGF-$\beta$2 (n=5). Thus, dominant TGF-$\beta$ isoforms were completely opposite between human and bovine colostrum samples. The concentrations of both isoforms declined as lactation proceeded. Biological activities of the colostrum samples were determined using an MV1LU cell line. Consistent with the result from the immunoassay, TGF-$\beta$1 in human and TGF-$\beta$2 in bovine colostrum were responsible for the anti proliferative activity against MV1LU cells. Furthermore, bovine colostrum increased IgA secretion by LPS-stimulated mesenteric lymph node (MLN) cells, and this effect was abrogated by either anti­TGF-$\beta$2 antibody or combined anti-TGF-$\beta$1/$\beta$2 antibody, but not by anti- TGF-$\beta$1 antibody alone. Similarly, TGF-$\beta$2 in bovine colostrum enhanced the Ig germ line (GL) promoter activity, which is the earliest event toward IgA isotype switching. Taken together, these results suggest that TGF-$\beta$ isoforms, differentially expressed in human and bovine colostrum, may promote IgA isotype production in the neonatal intestine.

• Molecules and Cells
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• v.24 no.2
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• pp.283-287
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• 2007

$TGF-{\beta}1$ induces Ig germ-line ${\alpha}$ ($GL{\alpha}$) transcription and subsequent class switching recombination (CSR) to IgA. In the present study, we investigated the roles of two E3-ubiquitin ligases, Smurfs (HECT type) and Arkadia (RING finger type) on $TGF{\beta}1$-induced IgA CSR. We found that over-expression of Smurf1 and Smurf2 decreased $TGF{\beta}1$-induced $GL{\alpha}$ promoter activity and strengthened the inhibitory effect of Smad7 on the promoter activity. Further, over-expression of Smurf1 and Smurf2 decreased both Smad3/4-mediated and Runx3-mediated $GL{\alpha}$ promoter activities, suggesting that the Smurfs can down-regulate the major $TGF-{\beta}1$ signaling pathway and decrease $GL{\alpha}$ gene expression. In parallel, the over-expressed Smurf1 decreased the expression of endogenous IgA CSR-predictive transcripts ($GLT_{\alpha}$, $PST_{\alpha}$, and $CT_{\alpha}$) and also $TGF{\beta}1$-induced IgA secretion. Conversely over-expression of Arkadia abolished the inhibitory effect of Smad7 on $TGF{\beta}1$-induced $GLT_{\alpha}$ expression and IgA secretion. Similar results were obtained in the presence of over-expressed Smad7 and Smurf1. These results indicate that Arkadia can amplify $TGF{\beta}1$-induced IgA CSR by degrading Smad7, which interacts with Smurf1. We conclude that Smurf and Arkadia have opposite roles in the regulation of $TGF{\beta}1$-induced IgA isotype expression.

• 한국생물공학회:학술대회논문집
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• 2005.10a
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• pp.682-682
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• 2005

• Hanyang Medical Reviews
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• v.33 no.1
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• pp.10-16
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• 2013

Follicular helper T cells (Tfh) play a significant role in providing T cell help to B cells during the germinal center reaction, where somatic hypermutation, affinity maturation, isotype class switching, and the differentiation of memory B cells and long-lived plasma cells occur. Antigen-specific T cells with IL-6 and IL-21 upregulate CXCR5, which is required for the migration of T cells into B cell follicles, where these T cells mature into Tfh. The surface markers including PD-1, ICOS, and CD40L play a significant role in providing T cell help to B cells. The upregulation of transcription factor Bcl-6 induces the expression of CXCR5, which is an important factor for Tfh differentiation, by inhibiting the expression of other lineage-specific transcription factors such as T-bet, GATA3, and RORγt. Surprisingly, recent evidence suggests that CD4 T cells already committed to Th1, Th2, and Th17 cells obtain flexibility in their differentiation programs by downregulating T-bet, GATA3, and RORγt, upregulating Bcl-6 and thus convert into Tfh. Limiting the numbers of Tfh within germinal centers is important in the regulation of the autoantibody production that is central to autoimmune diseases. Recently, it was revealed that the germinal center reaction and the size of the Tfh population are also regulated by thymus-derived follicular regulatory T cells (Tfr) expressing CXCR5 and Foxp3. Dysregulation of Tfh appears to be a pathogenic cause of autoimmune disease suggesting that tight regulation of Tfh and germinal center reaction by Tfr is essential for maintaining immune tolerance. Therefore, the balance between Tfh and Tfr appears to be a critical peripheral tolerance mechanism that can inhibit autoimmune disorders.

• Journal of Haehwa Medicine
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• v.16 no.2
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• pp.147-169
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• 2007

To evaluate the therapeutic effects of BGG on atopic dermatitis, we investigated the composition of immune cells of lymph node, PBMC and skin of Dermatophagoides farinae-induced NC/Nga mice. The levels of immunoglobulins in serum were analyzed at the protein level and the amount of pathologic cytokines were investigated using CD3/CD28 stimulated splenocytes. The results are summarized below; 1. BGG showed no cytotoxic effect up to $200\;{\mu}g/m{\ell}$ on mLFC in vitro. 2. BGG showed no hepatotoxicity in vivo based on the levels of ALT and AST. 3. Atopic dermatitis was improved through naked eye examination. BGG reduced the skin clinical index from 2.9 to 1.3 (p<0.01). 4. H&E and toluidine blue staining of tissue biopsies revealed that BGG inhibited the infiltration of lymphocytes and mast cells to skin. 5. BGG reduced the number of CD19 positive B cells in PBMCs by 16% (p<0.01), whereas cells were increased by 26% (p<0.05) in lymph nodes. 6. BGG reduced the numbers of B220+/CD23+ cells by 15% (p<0.01) and 33% in PBMCs and lymph node, respectively. 7. BGG reduced the numbers of B220+/IgE+ cells in PBMCs and lymph node by 21% and 33% (p<0.01), respectively. 8. BGG suppressed the levels of IgE (13%, p<0.001) as well as IgM (34%, p<0.001), IgG2a (40%, p<0.001) and IgG2b (26%, p<0.05). 9. BGG reduced the levels of IL-4 and IFN-$\gamma$ by 7% (p<0.05) and 13% (p<0.001) in anti-CD3 and anti-CD28-activated splenocytes, respectively. 10. BGG considerably inhibited the production of TNF-$\alpha$ and IL-6 by 42% (p<0.01) and 15% in the serum, respectively. Based on the results above, we concluded that BGG has therapeutic effects on atopic dermatitis by regulating the differentiation of B cells and isotype switching of IgE. Further investigations on the molecular mechanisms of BGG on atopic dermatitis are anticipated.