التفاصيل البيبلوغرافية
| العنوان: |
Endosomal sequestration of TLR4 antibody induces myeloid-derived suppressor cells and reverses acute Type 1 Diabetes |
| المؤلفون: |
Ada Admin (8524211), Kathryn C.S. Locker (11831126), Kritika Kachapati (7828964), Yuehong Wu (4889893), Kyle J. Bednar (6489944), David Adams (202540), Carolyn Patel (11831133), Hiroki Tsukamoto (4335766), Luke S Heuer (11831138), Bruce J. Aronow (11202042), Andrew B. Herr (333264), William M. Ridgway (7828976) |
| سنة النشر: |
2022 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biological Sciences not elsewhere classified, Myeloid-derived Suppressor Cells, Autoimmune Responses, Immune Regulation, Type 1 Diabetes, Non-Obese Diabetic (NOD) Mouse |
| الوصف: |
We previously showed that treating NOD mice with an agonistic monoclonal anti-TLR4/MD2 antibody (TLR4-Ab) reversed acute type one diabetes (T1D). Here, we show that TLR4-Ab reverses T1D by induction of myeloid derived suppressor cells (MDSC). Unbiased gene expression analysis after TLR4-Ab treatment demonstrated upregulation of genes associated with CD11b+Ly6G+ myeloid cells, and downregulation of T cell genes. Further RNAseq of purified, TLR4-Ab treated CD11b+ cells showed significant upregulation of genes associated with bone marrow-derived CD11b+ cells and innate immune system genes. TLR4-Ab significantly increased percentages and numbers of CD11b+ cells. TLR4-Ab-induced CD11b+ cells, derived ex vivo from TLR4-Ab treated mice, suppress T cells, and TLR4-Ab-conditioned bone marrow cells suppress acute T1D when transferred into acutely diabetic mice. Thus, the TLR4-Ab-induced CD11b+ cells, by currently accepted definition, are MDSCs able to reverse T1D. To understand the TLR4-Ab mechanism we compared TLR4-Ab to TLR4 agonist LPS (which cannot reverse T1D). TLR4-Ab remains sequestered at least 48 times longer than LPS within early endosomes, alters TLR4 signaling and downregulates inflammatory genes and proteins including NFkB. TLR4-Ab in the endosome therefore induces a sustained, attenuated inflammatory response providing an ideal “second signal” for the activation/maturation of MDSCs that can reverse acute T1D. |
| نوع الوثيقة: |
still image |
| اللغة: |
unknown |
| العلاقة: |
https://figshare.com/articles/figure/Endosomal_sequestration_of_TLR4_antibody_induces_myeloid-derived_suppressor_cells_and_reverses_acute_Type_1_Diabetes/17185826Test |
| DOI: |
10.2337/figshare.17185826.v1 |
| الإتاحة: |
https://doi.org/10.2337/figshare.17185826.v1Test |
| حقوق: |
CC BY-NC-SA 4.0 |
| رقم الانضمام: |
edsbas.70034291 |
| قاعدة البيانات: |
BASE |
