지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2013.10
- 수록면
- 194 - 198 (5page)
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초록· 키워드
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Recent papers have shown that the initial event in the pathogenesis of autoimmune type 1 diabetes (T1D) comprises sensing of molecular patterns released from apoptotic β-cells by innate immune receptors such as toll-like receptor (TLR). We have reported that apoptotic β-cells undergoing secondary necrosis called ‘late apoptotic’ β-cells stimulate dendritic cells (DCs) and induce diabetogenic T cell priming through TLR2. The role of other innate immune receptors such as TLR7 or TLR9 in the initiation of T1D has also been suggested. We hypothesized that TLR2 blockade could inhibit T1D at the initial step of T1D. Indeed, when a TLR2 agonist, Pam3CSK₄ was administered chronically, the development of T1D in nonobese diabetic (NOD) mice was inhibited. Diabetogenic T cell priming by DCs was attenuated by chronic treatment with Pam3CSK₄, indicating DC tolerance. For the treatment of established T1D, immune tolerance alone is not enough because β-cell mass is critically reduced. We employed TLR2 tolerance in conjunction with islet transplantation, which led to reversal of newly established T1D. Dipeptidyl peptidase 4 (DPP4) inhibitors are a new class of anti-diabetic agents that have beneficial effects on β-cells. We investigated whether a combination of DPP4 inhibition and TLR2 tolerization could reverse newly established T1D without islet transplantation. We could achieve normoglycemia by TLR2 tolerization in combination with DPP4 inhibition but not by TLR2 tolerization or DPP4 inhibition alone. β-cell mass was significantly increased by combined treatment with TLR2 tolerization and DPP4 inhibition. These results suggest the possibility that a novel strategy of TLR tolerization will be available for the inhibition or treatment of established T1D when combined with measures increasing critically reduced β-cell mass of T1D patients such as DPP4 inhibition or stem cell technology.
목차
INTRODUCTION
β-CELL APOPTOSIS AS A MECHANISM OF DIABETOGENIC T CELL SENSITIZATION IN T1D
INHIBITION OF T1D BY TLR2 TOLERANCE
TREATMENT OF ESTABLISHED T1D BY TLR2 TOLERANCE IN CONJUNCTION WITH MEASURES INCREASING β-CELL MASS
CONCLUSION
REFERENCES
참고문헌 (16)
참고문헌 신청
1. [학술지(정기간행물)] - Kim, Y. -H. / 1999 / Apoptosis of pancreatic β-cells detected in accelerated diabetes of NOD mice:no role of Fas-Fas ligand interaction in autoimmune diabetes / Eur. J. Immunol 29 : 455 ~ 465
2. [학술지(정기간행물)] - O’Brien, B. A. / 1997 / Apoptosis is the mode of β-cell death responsible for the development of IDDM in the nonobese diabetic (NOD) mouse / Diabetes 46 : 750 ~ 757
3. [학술지(정기간행물)] - Finegood, D. T. / 2001 / β-cell mass dynamics in Zucker Diabetic Fatty rats / Diabetes 50 : 1021 ~ 1029
4. [학술지(정기간행물)] - Trudeau, J. D. / 2000 / Neonatal beta-cell apoptosis: a trigger for autoimmune diabetes? / Diabetes 49 : 1 ~ 7
5. [학술지(정기간행물)] - Kim, H. S. / 2007 / Toll-like receptor 2 senses beta-cell death and contributes to the initiation of autoimmune diabetes / Immunity 27 : 321 ~ 333
2. [학술지(정기간행물)] - O’Brien, B. A. / 1997 / Apoptosis is the mode of β-cell death responsible for the development of IDDM in the nonobese diabetic (NOD) mouse / Diabetes 46 : 750 ~ 757
3. [학술지(정기간행물)] - Finegood, D. T. / 2001 / β-cell mass dynamics in Zucker Diabetic Fatty rats / Diabetes 50 : 1021 ~ 1029
4. [학술지(정기간행물)] - Trudeau, J. D. / 2000 / Neonatal beta-cell apoptosis: a trigger for autoimmune diabetes? / Diabetes 49 : 1 ~ 7
5. [학술지(정기간행물)] - Kim, H. S. / 2007 / Toll-like receptor 2 senses beta-cell death and contributes to the initiation of autoimmune diabetes / Immunity 27 : 321 ~ 333
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UCI(KEPA) : I410-ECN-0101-2016-511-001745758