Editors' ChoiceImmunology

Mice May Not Be Liars After All

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Science Translational Medicine  08 Aug 2012:
Vol. 4, Issue 146, pp. 146ec140
DOI: 10.1126/scitranslmed.3004702

For centuries, scientists have used animal (nonhuman) disease models to test hypotheses and determine drug safety before they are used in the clinic. However, there are fundamental limitations of animal models, and clearly, the mouse differs from a human in more ways than sheer size. Rather than belaboring these differences between mice and men, Haniffa and co-workers looked into the mouse immune system to identify any similarities that could suggest that such models are, indeed, true representatives of man.

In their new study, Haniffa et al. provide data that may align the immune response of mouse and human. The team not only found similarities, but also described for the first time a subset of cells in mice called dendritic cells (DCs) that share similar structural and behavioral characteristics with their human DC counterpart. DCs play an important role in starting effective and maintaining efficient immune responses; without these cells, combating infections and cancer would be virtually impossible. The authors relied on molecular and cellular imaging to compare the markers expressed on the surface of DCs (CD141 and CD103) both in human and in mouse, respectively. These proteins seem to have equal functional roles in both organisms and are expressed by DCs located mostly in the skin, the lungs, and other nonlymphoid tissues. Like human DCs, these cells have the capacity to proliferate and migrate to lymphoid organs, where they further participate in the maturation of lymphocytes. The fundamental difference of these human cells with DCs located in peripheral organs is their superior capacity for triggering immune responses against soluble antigens (cross-presentation).

This study sheds light on the intrinsic immunological similarities between the human and mouse immune systems and provides new hopes for using mice as reliable models to assess the effect of new therapeutics and to understand the basic principles of immune regulation. The similarities, such as this one uncovered by Haniffa, may be the norm rather than the exception, begging the translational question: Which other features of the immune response between mice and human could be used to design better disease models?

M. Haniffa et al., Human tissues contain CD141hi cross-presenting dendritic cells with functional homology to mouse CD103+ nonlymphoid dendritic cells. Immunity 37, 60–73 (2012). [Abstract]

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