Adaptation of Innate Lymphoid Cells to a Micronutrient Deficiency Promotes Type 2 Barrier Immunity
Open accessAbstract
How the immune system adapts to malnutrition to sustain immunity at barrier surfaces, such as the intestine, remains unclear. Vitamin A deficiency is one of the most common micronutrient deficiencies and is associated with profound defects in adaptive immunity. Here, we found that type 3 innate lymphoid cells (ILC3s) are severely diminished in vitamin A–deficient settings, which results in compromised immunity to acute bacterial infection. However, vitamin A deprivation paradoxically resulted in dramatic expansion of interleukin-13 (IL-13)–producing ILC2s and resistance to nematode infection in mice, which revealed that ILCs are primary sensors of dietary stress. Further, these data indicate that, during malnutrition, a switch to innate type 2 immunity may represent a powerful adaptation of the immune system to promote host survival in the face of ongoing barrier challenges.
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Depletion of vitamin A, in the adult, led to a decrease of Th1, Th17, and ILC3 responses, an effect which is counteracted through time.
“the depletion of vitamin A, in the adult, led to a decrease of Th1, Th17, and ILC3 responses (a synonym of lowered immunity to bacterial infection), an effect which is counteracted through time127.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [127]
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- Authors
- Spencer, S. P., Wilhelm, C., Yang, Q., Hall, J. A., Bouladoux, N., Boyd, A., Nutman, T. B., Urban, J. F., Wang, J., Ramalingam, T. R., Bhandoola, A., Wynn, T. A., & Belkaid, Y.
- Affiliations
- National Institutes of Health (US)
- University of Pennsylvania (US)
- Helminth Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, NIH, Bethesda, MD 20892, USA.
- Beltsville Human Nutrition Research Center (US)
- University of California, Berkeley (US)
- Corresponding author
- Spencer, S. P.
- Wilhelm, C.
- Belkaid, Y.
- Venue
- Science
- Published
- 2014-01-24
- Volume
- 343
- Issue
- 6169
- Pages
- 432-437
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4313730
- OpenAlex
- W1999696784
- Cited by
- 447
- References
- 38
- Citations by year
- 2026: 14 · 2025: 23 · 2024: 25 · 2023: 31 · 2022: 33 · 2021: 24 · 2020: 29 · 2019: 44 · 2018: 36 · 2017: 43 · 2016: 40 · 2015: 56 · 2014: 48 · 2012: 1
- FWCI
- 28.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 AI999999)
- National Institute of Diabetes and Digestive and Kidney Diseases (F30DK094708)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- innate lymphoid cells, vitamin A deficiency, micronutrient deficiency, malnutrition, Th2 immune response, ILC3, ILC2, IL-13, intestinal immunity, barrier immunity, nematode infection, acute bacterial infection, immune adaptation
- MeSH terms
- Animals, Enterobacteriaceae Infections, Immunity, Innate, Lymphocytes, Mice, Inbred C57BL, Mice, Mutant Strains, Vitamin A, Vitamin A Deficiency, Homeodomain Proteins, Interleukin-13, Micronutrients, Citrobacter rodentium, Mice, Adaptive Immunity
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