Volume 10 Issue 2, February 2009

Type 1 diabetes is an immune-mediated disease in which pancreatic insulin-producing beta cells are damaged and destroyed. Animal models have served a prominent function in the development of the present ideas of pathogenesis and approaches to therapy. This commentary addresses the utility and limitations of these models for facilitating the 'translation' of immunology research into clinical applications.

The transcription factor Foxo1 regulates the homeostasis of naive peripheral T cells by 'translating' nutrient-availability signals into the expression of lymphoid tissue–homing molecules and the receptor for interleukin 7.

Autophagy has been linked to inflammatory bowel disease. Studies of two different mouse strains deficient in the autophagy-related gene product Atg16L1 now show that autophagy is important in regulating the secretory function of Paneth cells and the production of inflammatory cytokines in the intestine.

Compared with that of naive CD8⁺ T cells, the homeostatic population expansion of naive CD4⁺ T cells in a lymphopenic environment is limited. New data indicate that this difference is caused by high systemic concentrations of IL-7, which inhibit the function of dendritic cells.

The multifarious fates of CD4⁺ T helper cells mediate helpful and harmful immunity. An unexpected kinship between 'harmful' interleukin 17–producing T helper cells and 'helpful' follicular T helper cells has now been found.

Compared with naive CD8+ T cells, naive CD4⁺ T cells undergo inefficient homeostatic proliferation. Mackall and colleagues now attribute this difference to interleukin 7–mediated suppression of the expression of MHC class II on dendritic cells.

The mechanism by which the coreceptor CD28 contributes to T cell activation is vague. Ghosh and colleagues find that CD28 facilitates NF-κB activation by regulating recruitment and phosphorylation of the kinase PDK1.

The costimulatory molecule ICOS is important for the development of both interleukin 17–producing and follicular T helper cells. Kuchroo and colleagues find that ICOS induces the transcription factor c-Maf, which regulates the population expansion of both helper cell types.

Factors governing T cell homeostasis are poorly defined. Hedrick and colleagues find that the transcription factor Foxo1 maintains the homeostasis of naive T cells by regulating genes involved in T cell trafficking and survival.

Leukocyte adhesion is governed by the affinity state of integrin LFA-1. Laudanna and colleagues show that many Rho GTPase family members interact to form a regulatory module that regulates LFA-1 activation.

Hypoxia incites inflammation, particularly at mucosal surfaces. Eltzschig and colleagues show that hypoxia also suppresses inflammation by inducing expression of the neuronal guidance molecule netrin-1, which inhibits the transepithelial migration of neutrophils.

The C-type lectin dectin-1 induces T cell responses. Geijtenbeek and colleagues demonstrate that in human dendritc cells, dectin-1 ligands induce two independent signaling pathways that act in synergy at the point of activation of nuclear factor-κB.

The adaptor Fc receptor common γ-chain transduces signals for many immunoreceptors. Taki and colleagues find that this adaptor 'reroutes' interleukin 3 signals to induce interleukin 4 production and T helper 2 differentiation.