JDRF Request for Applications: Development of Interventions to Modulate Immune Cell Trafficking in T1D

Funding over a maximum of three years for clinical or preclinical projects to identify and validate reagents that promote immune rebalance and the protection of pancreatic beta cell function through modulating the trafficking of immune cells to the pancreatic islets.

JDRF, based in the United States, is an international organisation that funds innovative research to advance the treatment, prevention and cure of type-1 diabetes (T1D).

This Request for Applications – ‘Development of Interventions to Modulate Immune Cell Trafficking in T1D’ – is seeking proposals for research to identify and validate reagents that promote immune rebalance and the protection of beta cell function through modulating the trafficking of proinflammatory or autoreactive cells to the pancreatic islets.

Limiting and blocking immune trafficking to the islets has not been extensively evaluated in human relevant models. The identification and validation of novel strategies to target islet homing pathways while avoiding broad immunosuppression is of high interest for this funding opportunity.

While it is generally understood that T1D is caused by damage to islets in pancreatic beta calls caused by abnormal immune response, the actual mechanism that initiates TID is unknown. It is thought that impaired immunoregulation and a loss of self-tolerance allows for the survival and propagation of autoreactive cells that infiltrate pancreatic islets and attack insulin-producing beta cells.

The fundamental steps involved in the process of lymphocytes exiting circulation and entering tissue in the body (extravasation) each serve as a potential target for intervention, and a blockade at any step could inhibit the extravasation process. One potential strategy for preventing the autoimmune attack on beta cells is to inhibit immune trafficking to the pancreas and islets, such as by blockading selectins or neutralising/knocking out chemokines.

Examples of proposals that would be considered under this call include, but are not limited

to:

• Development or validation of reagents that target receptors (eg chemokines receptors, sphingolipids receptors, etc) or adhesion molecules involved in the trafficking of pro- inflammatory and/or autoreactive immune cells to the pancreas (approaches that have been previously tested in T1D must be incremental and evaluated at the next stage of development).
• Realignment of mechanisms and clinical grade reagents involved in cell trafficking validated in other diseases for assessment in T1D.

Priority will be given to approaches that:

• Propose methods of targeting cell trafficking while avoiding broad immunosuppression.
• Validation of reagents in T1D that have been clinically evaluated in other disease indications.
• Projects that include research protocols utilising human samples or human relevant model systems.

Proposals should describe the preclinical or clinical development of therapeutic strategies targeting the trafficking of disease-relevant immune cell populations.