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Glucocorticoid-induced TNF receptor family-related protein (GITR) regulates the function of both T cells and antigen-presenting cells (APCs), while the function of GITR ligand (GITR-L) is largely unknown. Here we evaluate the role of GITR-L, whose expression is restricted to APCs, in the development of enterocolitis. On injecting naive CD4+ T cells, GITR-L-/- Rag-/- mice develop a markedly milder colitis than Rag-/- mice, which correlates with a 50% reduction of Ly6C+CD11b+MHCII+ macrophages in the lamina propria and mesenteric lymph nodes. The same result was observed in αCD40-induced acute colitis and during peritonitis, suggesting an altered monocyte migration. In line with these observations, the number of nondifferentiated monocytes was approximately 3-fold higher in the spleen of GITR-L-/-Rag-/- mice than in Rag-/- mice after αLCD40 induction. Consistent with the dynamic change in the formation of an active angiotensin 1I type 1 receptor (AT1) dimer in GITR-L-/- splenic monocytes during intestinal inflammation, the migratory capability of splenic monocytes from GITR-L-deficient mice was impaired in an in vitro transwell migration assay. Conversely, αGITR-L reduces the number of splenic Ly6Chi monocytes, concomitantly with an increase in AT1 dimers. We conclude that GITR-L regulates the number of proinflammatory macrophages in sites of inflammation by controlling the egress of monocytes from the splenic reservoir. [ABSTRACT FROM AUTHOR]

Objectives: In a community randomized trial, we aimed to promote exclusive breastfeeding and appropriate complementary feeding practices in under-twos to ascertain the feasibility of using available channels for nutrition counselling, their relative performance and the relationship between intensity of counselling and behaviour change. We also assessed whether using multiple opportunities to impart nutrition education adversely affected routine activities.Methods: We conducted a community randomized, controlled effectiveness trial in rural Haryana, India, with four intervention and four control communities. We trained health and nutrition workers in the intervention communities to counsel mothers at multiple contacts on breastfeeding exclusively for 6 months and on appropriate complementary feeding practices thereafter. The intervention was not just training health and nutrition workers in counselling but included community and health worker mobilization.Findings: In the intervention group, about 32% of caregivers were counselled by traditional birth attendants at birth. The most frequent sources of counselling from birth to 3 months were immunization sessions (45.1%) and home visits (32.1%), followed closely by weighing sessions (25.5%); from 7 to 12 months, home visits (42.6%) became more important than the other two. An increase in the number of channels through which caregivers were counselled was positively associated with exclusive breastfeeding prevalence at 3 months (p = 0.002), consumption of milk/cereal gruel or mix use at 9 months (p = 0.004) and 18 months (p = 0.003), undiluted milk at 9 months (p<0.0001) and 24 hour non-breast-milk energy intakes at 18 months (p = 0.023), after controlling for potential confounding factors. Intervention areas, compared with the control, had higher coverage for vitamin A (45% vs. 11.5%) and iron folic acid (45% vs. 0.4%) supplementation.Conclusions: Using multiple available opportunities and workers for counselling caregivers was feasible, resulted in high coverage and impact, and instead of disrupting ongoing services, resulted in their improvement. [ABSTRACT FROM AUTHOR]

According to the ‘hygiene hypothesis’, enhanced microbial exposure due to early childhood infections leads to a reduction of Th2-mediated allergic diseases and inflammatory bowel disease. To begin to elucidate the mechanisms underlying this hypothesis, we studied development of Th2-mediated colitis of the TCRα knockout (KO) mouse in both a specific pathogen-free (SPF) facility and a conventional (CV) facility. After more than five generations in each facility, TCRα KO mice kept in the CV facility developed dramatically less colitis than mice that were kept in the SPF facility. Surprisingly, the suppression of colitis in the CV facility correlated with a significant increase in natural IgM production by B-1 B cells. In contrast, B cell-deficient TCRα double-knockout (αμ DKO) mice maintained in the CV facility continued to develop severe colitis, strongly suggesting that B-1 B cells contributed to the suppression of colitis. Indeed, the adoptive transfer of B-1 B cells isolated from the peritoneal cavity of TCRα KO mice (SPF) into αμ DKO mice (CV) suppressed the development of colitis in the recipient mice. We conclude that B-1 cells play a regulatory role in Th2-mediated colitis under non-hygienic conditions, possibly by generating natural antibodies in response to microbial flora. [ABSTRACT FROM AUTHOR]