A PHP Error was encountered

Severity: Warning

Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests

Filename: helpers/my_audit_helper.php

Line Number: 143

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML

File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Attempt to read property "Count" on bool

Filename: helpers/my_audit_helper.php

Line Number: 3100

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

A hydrogel platform for co-delivery of immunomodulatory proteins for pancreatic islet allografts. | LitMetric

AI Article Synopsis

  • * T cells are crucial in transplant rejection, and research suggests that manipulating the balance between harmful T effector cells and protective T regulatory cells could improve outcomes, potentially allowing for transplantation without systemic immune suppression.
  • * A new hydrogel delivery system was developed to target both T cell types, showing promise in promoting local immune tolerance, but ultimately, it didn't achieve indefinite allograft survival due to the presence of Granzyme B-expressing CD

Article Abstract

Type 1 diabetes (T1D), an autoimmune disorder in which the insulin-producing β-cells in the islets of Langerhans in the pancreas are destroyed, afflicts over 1.6 million Americans. Although pancreatic islet transplantation has shown promise in treating T1D, continuous use of required immunosuppression regimens limits clinical islet transplantation as it poses significant adverse effects on graft recipients and does not achieve consistent long-term graft survival with 50%-70% of recipients maintaining insulin independence at 5 years. T cells play a key role in graft rejection, and rebalancing pathogenic T effector and protective T regulatory cells can regulate autoimmune disorders and transplant rejection. The synergy of the interleukin-2 (IL-2) and Fas immunomodulatory pathways presents an avenue for eliminating the need for systemic immune suppression by exploiting IL-2's role in expanding regulatory T cells and leveraging Fas ligand (FasL) activity on antigen-induced cell death of effector T cells. Herein, we developed a hydrogel platform for co-delivering an analog of IL-2, IL-2D, and FasL-presenting microgels to achieve localized immunotolerance to pancreatic islets by targeting the upregulation of regulatory T cells and effector T cells simultaneously. Although this hydrogel provided for sustained, local delivery of active immunomodulatory proteins, indefinite allograft survival was not achieved. Immune profiling analysis revealed upregulation of target regulatory T cells but also increases in Granzyme B-expressing CD8 T cells at the graft site. We attribute the failed establishment of allograft survival to these Granzyme B-expressing T cells. This study underscores the delicate balance of immunomodulatory components important for allograft survival - whose outcome can be dependent on timing, duration, modality of delivery, and disease model.

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbm.a.37429DOI Listing

Publication Analysis

Top Keywords

regulatory cells
16
allograft survival
12
cells
9
hydrogel platform
8
immunomodulatory proteins
8
pancreatic islet
8
islet transplantation
8
effector cells
8
granzyme b-expressing
8
platform co-delivery
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: