Tuesday, September 12, 2017

It is really hard to replicate human autoimmune diseases in mice

A new study in PNAS highlights the challenges scientists face when trying to reproduce human diseases in mice.  

Here, the authors tried to reproduce human type I diabetes by creating humanized mice by transplantation of HLA-DQ8+ human fetal thymus and CD34+ stem cells into immunodeficient mice (to recreate human immune system in mouse) followed by transfer of autologous [hu-mice]-derived HLA-DQ8/insulin-B:9–23 specific TCR transduced human CD4+ T cells and followed by two successive low doses of streptozotocin (a chemical to damage islet β cells and release auto-antigen).

However, even these steps were not enough to induce diabetes in hu-mice. Only immunization with insulin B:9–23 peptide + adjuvant (HLA class II-restricted T-cell response to InsB:9–23 peptide is highly associated with T1D in humans) in addition to above mentioned "conditioning" were able to induce diabetes in hu-mice.

No one really knows how autoimmune diseases are initiated in humans and these study shows that it is really hard to "reproduce" it in mice. Of course, it is not known what factors could play the role of "streptozotocin" and "B:9–23 peptide immunization" in natural context in humans. 

posted by David Usharauli

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