Intestinal microbes influence development of thymic lymphocytes in early life.

The thymus generates cells of the T cell lineage that seed the lymphatic and blood systems. Transcription factor regulatory networks control the lineage programming and maturation of thymic precursor cells. Whether extrathymic antigenic events, such as the microbial colonization of the mucosal tract also shape the thymic T cell repertoire is unclear. We show here that intestinal microbes influence the thymic homeostasis of PLZF-expressing cells in early life. Impaired thymic development of PLZF+ innate lymphocytes in germ-free (GF) neonatal mice is restored by colonization with a human commensal, Bacteroides fragilis, but not with a polysaccharide A (PSA) deficient isogenic strain. Plasmacytoid dendritic cells influenced by microbes migrate from the colon to the thymus in early life to regulate PLZF+ cell homeostasis. Importantly, perturbations in thymic PLZF+ cells brought about by alterations in early gut microbiota persist into adulthood and are associated with increased susceptibility to experimental colitis. Our studies identify a pathway of communication between intestinal microbes and thymic lymphocytes in the neonatal period that can modulate host susceptibility to immune-mediated diseases later in life.

Understanding delays to parathyroidectomy: A mixed-methods approach.

BACKGROUND: Patients from ethnic and racial minority groups with primary hyperparathyroidism may have greater time delays to curative parathyroidectomy. Contributing factors are unclear. METHODS: This was a sequential mixed-methods study. The quantitative phase was a retrospective chart review of adults with primary hyperparathyroidism who underwent parathyroidectomy between 2015 and 2020, collecting demographic and clinical data. Social vulnerability of the patients' residential area, measured with the Social Vulnerability Index, and relevant clinical time intervals were calculated. A multivariable analysis of factors associated with greater time intervals was performed. The qualitative phase involved semistructured interviews with endocrinologists, analyzed inductively for themes. RESULTS: On chart review of 1,083 patients, the median age was determined to be 61 years and 856 (79%) were female. Six hundred twenty-eight (57.9%) were non-Hispanic White and 456 (42.1%) were Hispanic ethnicity or Asian, Pacific Islander, Black, Native American, Other or Unknown race. Patients of Hispanic ethnicity, or Asian or Pacific Islander, Black, Native American, Other or Unknown race were more likely than non-Hispanic White patients to live in the most socially vulnerable areas (19.3% vs 5.9%, P < .01) and had greater time intervals than non-Hispanic White patients between index hypercalcemia and first parathyroid hormone level, surgical referral, or parathyroidectomy (all P < .05). On multivariable analysis, age (coefficient 7.9, 95% CI 2.8-13.0) and living in the most socially vulnerable areas (coefficient 297.9, 95% CI 87-508.7) were associated with greater days between index hypercalcemia and parathyroidectomy. In the study's qualitative phase, identified themes for reasons for care delays included socioeconomic, nonsocioeconomic patient, and nonsocioeconomic nonpatient factors. CONCLUSION: Care delays are driven by a combination of socioeconomic and nonsocioeconomic factors.