Medullary thymic epithelial cells (mTECs) play a pivotal role in the establishment of self-tolerance in T cells by ectopically expressing various tissue-restricted self-Ags and by chemoattracting developing thymocytes. The nuclear protein Aire expressed by mTECs contributes to the promiscuous expression of self-Ags, whereas CCR7-ligand (CCR7L) chemokines expressed by mTECs are responsible for the attraction of positively selected thymocytes. It is known that lymphotoxin signals from the positively selected thymocytes preferentially promote the expression of CCR7L rather than Aire in postnatal mTECs. However, it is unknown how lymphotoxin signals differentially regulate the expression of CCR7L and Aire in mTECs and whether CCR7L-expressing mTECs and Aire-expressing mTECs are distinct populations. In this study, we show that the majority of postnatal mTECs that express CCL21, a CCR7L chemokine, represent an mTEC subpopulation distinct from the Aire-expressing mTEC subpopulation. Interestingly, the development of CCL21-expressing mTECs, but not Aire-expressing mTECs, is impaired in mice deficient in the lymphotoxin β receptor. These results indicate that postnatal mTECs consist of heterogeneous subsets that differ in the expression of CCL21 and Aire, and that lymphotoxin β receptor regulates the development of the CCL21-expressing subset rather than the Aire-expressing subset of postnatal mTECs.

Background There is controversy regarding the potential influence of vitamin D deficiency, exposure to environmental tobacco smoke, BCG vaccination, season, and body habitus on susceptibility to Mycobacterium tuberculosis (MTB) infection. Methods We conducted a cross-sectional analysis to identify determinants of a positive QuantiFERON-TB Gold (QFT) assay result in children aged 6–13 years attending 18 schools in Ulaanbaatar, Mongolia. Data relating to potential risk factors for MTB infection were collected by questionnaire, physical examination, and determination of serum 25-hydroxyvitamin D (25[OH]D) concentrations. Risk ratios (RRs) were calculated with adjustment for potential confounders, and population attributable fractions (PAFs) were calculated for modifiable risk factors identified. Results Nine hundred forty-six of 9810 (9.6%) participants had a positive QFT result. QFT positivity was independently associated with household exposure to pulmonary tuberculosis (adjusted RR [aRR], 4.75 [95% confidence interval {CI}, 4.13–5.46, P < .001]; PAF, 13.1% [95% CI, 11.1%–15.0%]), vitamin D deficiency (aRR, 1.23 [95% CI, 1.08–1.40], P = .002; PAF, 5.7% [95% CI, 1.9%–9.3%]), exposure to environmental tobacco smoke (1 indoor smoker, aRR, 1.19 [95% CI, 1.04–1.35]; ≥2 indoor smokers, aRR, 1.30 [95% CI, 1.02–1.64]; P for trend = .006; PAF, 7.2% [95% CI, 2.2%–12.0%]), and increasing age (aRR per additional year, 1.14 [95% CI, 1.10–1.19], P < .001). No statistically significant independent association was seen for presence of a BCG scar, season of sampling, or body mass index. Conclusions Vitamin D deficiency and exposure to environmental tobacco smoke are potentially modifiable risk factors for MTB infection.

The thymic medulla provides a microenvironment where medullary thymic epithelial cells (mTECs) contribute to the establishment of self-tolerance by the deletion of self-reactive T cells and the generation of regulatory T cells. The progression of thymocyte development critically regulates the optimum formation of the thymic medulla, as discussed in this article. Of note, it was recently identified that RANKL produced by positively selected thymocytes plays a major role in the thymocyte-mediated medulla formation. Indeed, transgenic expression of soluble RANKL increased the number of mTECs and enlarged the thymic medulla in mice. The effects of RANKL on the thymic medulla may be useful for the engineering of self-tolerance in T cells.

Population-based data relating to vitamin D status of children in Northeast Asia are lacking. We conducted a cross-sectional study to determine the prevalence and determinants of vitamin D deficiency in 9595 schoolchildren aged 6–13 years in Ulaanbaatar (UB), the capital city of Mongolia. Risk factors for vitamin D deficiency were collected by questionnaire, and serum 25-hydroxyvitamin D (25[OH]D) concentrations were measured using an enzyme-linked fluorescent assay, standardized and categorized as deficient (25[OH]D <10 ng/mL) or not. Odds ratios for associations between independent variables and risk of vitamin D deficiency were calculated using multivariate analysis with adjustment for potential confounders. The prevalence of vitamins D deficiency was 40.6% (95% CI 39.7% to 41.6%). It was independently associated with female gender (adjusted odds ratio [aOR] for girls vs. boys 1.23, 95% CI 1.11–1.35), month of sampling (aORs for December–February vs. June–November 5.28 [4.53–6.15], March–May vs. June–November 14.85 [12.46–17.74]), lower levels of parental education (P for trend <0.001), lower frequency of egg consumption (P for trend <0.001), active tuberculosis (aOR 1.40 [1.03–1.94]), household smoking (aOR 1.13 [1.02 to1.25]), and shorter time outdoors (P for trend <0.001). We report a very high prevalence of vitamin D deficiency among Mongolian schoolchildren, which requires addressing as a public health priority.