Wearing One's Own Coat

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Science  31 Aug 2007:
Vol. 317, Issue 5842, pp. 1147
DOI: 10.1126/science.317.5842.1147c

Autoimmunity conventionally falls within the realm of the adaptive immune system because it pertains to responses to self-constituents in humans and in a variety of animal models. Previous studies have shown that mice lacking the enzyme alpha-mannosidase-II (αM-II) exhibit a dearth of complex-type N-glycans and develop a syndrome similar to the human autoimmune disease systemic lupus erythematosus. Green et al. provide evidence that αM-II deficiency in mice involves activation of the innate immune system. The first piece of evidence emerged from the observation that initiation of disease did not require cells of hematopoietic origin; rather, the mesangial cells of the kidney were stimulated to produce inflammatory proteins. Subsequently, other cells of the innate immune system participated in the development of glomerulonephritis, which unexpectedly could be attenuated by boosting the adaptive immune system via injection of immunoglobulin G. The absence of αM-II resulted in a surfeit of hybrid-type N-glycans that were recognized by innate immune lectins otherwise dedicated to sensing the structurally similar mannose linkages of foreign glycoproteins. Future work might determine if the maturation of branched glycans on self-proteins broadly helps avert harmful innate immune responses, and whether pathogens might cloak themselves in complextype garb as a means of evading detection. — SJS

Immunity 27, 10.1016/j.immuni.2007.06.008 (2007).

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