Publications

Foxp3(+) regulatory T (Treg) cells limit pathogenic immune responses to self-antigens and foreign antigens. An essential role for microRNA (miRNA) in the maintenance and function of Treg cells, revealed by the Treg cell-specific Dicer ablation, raised a question as to a specific miRNA contribution. We found that Foxp3 controlled the elevated miR155 expression required for maintaining Treg cell proliferative activity and numbers under nonlymphopenic conditions. Moreover, miR155 deficiency in Treg cells resulted in increased suppressor of cytokine signaling 1 (SOCS1) expression accompanied by impaired activation of signal transducer and activator of transcription 5 (STAT5) transcription factor in response to limiting amounts of interleukin-2. Our studies suggest that Foxp3-dependent regulation of miR155 maintains competitive fitness of Treg cell subsets by targeting SOCS1, and they provide experimental support for a proposed role for miRNAs in ensuring the robustness of cellular phenotypes.

OBJECTIVES

To determine whether cognitive test scores and cognitive decline predict incidence of first diagnosed stroke.

DESIGN

Stroke-free Health and Retirement Study participants were followed on average 7.6 years for self- or proxy-reported first stroke (1,483 events). Predictors included baseline performance on a modified Telephone Interview for Cognitive Status (Mental Status) and Word Recall test and decline between baseline and second assessment in either measure. Hazard ratios (HRs) were estimated using Cox proportional hazards models for the whole sample and stratified according to five major cardiovascular risk factors.

SETTING

National cohort study of noninstitutionalized adults with a mean baseline age of 64+/-9.9.

PARTICIPANTS

Health and Retirement Study participants (n=19,699) aged 50 and older.

RESULTS

Word Recall (HR for 1 standard deviation difference=0.92, 95% confidence interval (CI)=0.86-0.97)) and Mental Status (HR=0.89, 95% CI=0.84-0.95) predicted incident stroke. Mental Status predicted stroke risk in those with (HR=0.93, 95%=0.87-0.99) and without (HR=0.81, 95% CI=0.72-.91) one or more vascular risk factors. Word Recall declines predicted a 16% elevation in subsequent stroke risk (95% CI=1.01-1.34). Declines in Mental Status predicted a 37% elevation in stroke risk (95% CI=1.11-1.70).

CONCLUSION

Cognitive test scores predict future stroke risk, independent of other major vascular risk factors.

The role of basophils, the rarest of blood granulocytes, in host immunity has been a mystery. Long considered the poor relative of mast cells, basophils have received much recent attention because of the availability of new reagents and models that reveal unique properties of these cells. Basophils are known to have distinct roles in allergic hypersensitivity reactions and in the immune response to intestinal helminthes. In this review, we highlight these advances and summarize our current understanding of the repertoire of functions attributed to these cells. Despite these recent insights, we are likely only beginning to gain a full understanding of how and where these cells lend effector functions to vertebrate immunity. Advances are likely to come only with the development of specific reagents that enable the finer study of basophil lineage and function. Although many fundamental aspects of basophil biology remain unanswered, the prospects remain bright for unmasking new contributions by these unusual cells.