Research Highlights

Anti-CD3/anti-CXCL10 combination therapy for type 1 diabetes.
(A) Local expression of CXCL10 and other chemo-kines in the islets of Langerhans as well as in the pancreatic lymph nodes drive the migration of leukocytes, including autoaggressive T cells to the islets. Due to b-cell destruction and stress the insulin production is insufficient to control the blood glucose level. (B) Anti-CD3 therapy causes a partial depletion of T cells and induces an immune balance shift resulting in a reduced insulitis and a temporarily restored insulin production. (C) However, in T1D patients anti-CD3 therapy only lasts for 1–2 years and in diabetic mice only about 30% go into remission. Regenerated T cells migrate to the islets and the self-destructive process start anew resulting in an impaired insulin production. (D) Administration of neutralizing anti-CXCL10 antibodies after the anti-CD3 therapy inhibits the migration of regenerated T cells and thereby prevents the re-infiltration of the islets resulting in a permanent T1D remission.


Christen U, Kimmel R. (2020) Chemokines as Drivers of the Autoimmune Destruction in Type 1 Diabetes: Opportunity for Therapeutic Intervention in Consideration of an Optimal Treatment Schedule.
Front. Endocrinol. 11:591083 

Islet transplantation under the kidnex capsule of diabetic mice.
CXCL10 influences the autoimmune destruction of islet isografts in mice with type 1 diabetes: Regulatory T cells (CD3+ (green) FoxP3+ (red)) in CXCL10-deficient intact pancreatic islet isografts on day 100 post-engraftment. Markedly increased number of Regulatory T cells was detected surrounding the islet isografts under the kidney capsule of non-diabetic mice.

Bender, C., Christen, S., Scholich, K., Bayer, M., Pfeilschifter, J.M., Hintermann, E., Christen, U. (2017) Islet-expressed CXCL10 promotes autoimmune destruction of islet iso-grafts in mice with type 1 diabetes. Diabetes 66:113-26 

Overview of hepatic cell interactions mediated by CAMs during liver inflammation and fibrosis. 

Displayed is a sinusoidal channel near a portal vein and a bile duct. (A) The microvessel is covered by activated hepatic stellate cells (HSCs), which act as mural cells. They interact with each other via N-cadherin and JAM-C homophilic binding and with sinusoidal endothelial cells (ECs) via JAM-B/JAM-C interaction. (B) HSCs are the main producers of fibrotic extracellular matrix (ECM), like collagen I. Tethered to the ECM is LAP-TGFb. Chemokine-attracted leukocytes get recruited to capillarized sinusoidal ECs by binding via integrins to members of the immunoglobulin (Ig) superfamily of cell adhesion molecules (IgCAMs) or to non-classical CAMs like VAP-1, or they bind to MAdCAM on vascular ECs before they transmigrate the endothelial wall and interact later on with (C) hepatocytes. (D) In biliary disease, also portal fibroblasts get activated, secret fibrotic ECM and bind to each other via JAM-C. Further, leukocytes attach to cholangiocytes e.g. via integrin/IgCAM binding. 

Hintermann E, Christen U. (2019) The Many Roles of Cell Adhesion Molecules in Hepatic Fibrosis. Cells 8: E1503 

Strong inflammation at an auxiliary site may act as filters for autoaggressive T-cells.
(A) Dynamic recirculation of both antigen-specific autoaggressive and unspecific bystander T-cells between the target site of autoimmune destruction (i.e. pancreas in T1D), lymphoid organs and auxiliary organs. Accumulation of autoaggressive T-cells at the target site causes active destruction of target cells (i.e. b-cells in T1D) and functional impairment (i.e. loss of insulin production in T1D). (B) Strong inflammation at an auxiliary site, for example by virus infection, might act as a filter for autoaggressive T-cells that might be drawn towards the newly infected site along chemokine gradients. Once arrived at the inflamed site they might die by hyperactivation induced apoptosis. Such a permanent removal of autoaggressive T-cells from the recirculating T-cell pool would abrogate the ongoing autoimmune destruction at the target site and restore its metabolic functions.

Christen, U. and von Herrath, M.G. (2005) Infection and Autoimmunity.

J. Immunol. 174 (12): 7481-7486. 

Cover Art

Clinical & Experimental Immunology; Issue 195; January 2019

Diabetes; Volume 66, Issue 1; January 2017

Annual Report 2002 - La Jolla Institute for Allergy and Immunology

Nature Immunology; Volume 3, Issue 10            October 2001