Specific microbiota direct the differentiation of Th17 cells in the mucosa of the small intestine

By I. Ivanov, Rosa de Frutos, N. Manel, K. Yoshinaga, D. Rifkin, R. Sartor, B. B. Finlay, Dan R. Littman. Cell Host and Microbe, 2008

1,737 citations recorded by the source corpus.

SUMMARY IL-17-producing T-helper cells (Th17) are potent effectors of inflammation, but little is known about the requirements for their differentiation in vivo at steady state. We found that specific commensal microbiota are required for Th17 cell differentiation in the lamina propria (LP) of the small intestine. Differentiation of Th17 cells correlated with presence of Cytophaga-Flavobacter-Bacteroidetes bacteria in the intestine, was independent of TLR, IL-21 or IL-23 signaling, but required appropriate activation of TGF-β. Absence of Th17 cell-inducing bacteria was accompanied by increased Foxp3+ regulatory T cells in the LP. Our results suggest that the composition of the microbiota regulates the Th17:Treg balance in the lamina propria and may thus influence intestinal immunity, tolerance, and susceptibility to inflammatory bowel diseases.

Subfields: Dermatology, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/85cdb897434c04668067ea1641efdd35c5d416fd

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Dermatology

1. Dan R. Littman
2. Hsin-jung Wu
3. Y. Belkaid
4. S. Mazmanian

In Immunology

1. Dan R. Littman
2. K. Honda
3. Y. Belkaid
4. G. Lee
5. Hsin-jung Wu
6. S. Mazmanian
7. Eric G. Pamer
8. T. Hand

In Molecular Biology

1. Y. Belkaid
2. Dan R. Littman
3. K. Honda
4. S. Mazmanian
5. F. Bäckhed
6. B. B. Finlay
7. Hsin-jung Wu
8. June L. Round

Citations in the corpus

• Th17 Cell Induction by Adhesion of Microbes to Intestinal Epithelial Cells (2015, neutral): “The gut microbiota contributes to the constitutive development of Th17 cells in the intestinal lamina propria (LP) (Atarashi et al., 2008; Ivanov et al., 2008).”
• Role of the Microbiota in Immunity and inflammation (2014, background): “…to most commensals that reside outside of the ‘‘demilitarized zone,’’ SFB interacts closely with the mucosal tissue via tight adhesion to Peyer’s patches and epithelial cells, inducing cytoskeletal reorganization in these cells at the site of contact (Ivanov et al., 2008; Sczesnak et al., 2011).”
• The gut microbiota regulates bone mass in mice (2012, background): “Interestingly, Th17 cell development is specifically affected by the gut microbiota, and GF mice are deficient in the production of IL-17 from CD4þ T cells, which is the signature cytokine of Th17 cells.((45)) Furthermore, GF mice display reduced Th17 cell numbers in the spleen and spinal cords.”
• Ischemia/Reperfusion (2016, neutral): “from energy regulation to cognitive function, with homeostasis maintained by the immune system (225,226,373).”
• Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells (2010, background): “…we compared their appearance through ontogeny: SI-LP Th17 cells arise abruptly between day 16 and day 25 after birth, around the time of weaning (Ivanov et al., 2008), which is just before the window of arthritis development previously reported for the K/BxN model, i.e., days 25–31 (Kouskoff et…”
• Microbial Dysbiosis in Colorectal Cancer (CRC) Patients (2011, background): “Some members of the gut microbiota may steer host T-cell responses [13,15] others may maintain homeostasis of effector helper T-cell populations in the gut [14].”
• The Human Microbiome: at the interface of health and disease (2012, background): “For example, Th17 cell differentiation in the mouse lamina propria requires the presence of segmented filamentous bacteria (SFB”
• Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease (2017, background): “Enhanced SFB adhesion on the epithelial induces the expression and release of serum amyloid A (SAA) from intestinal epithelial cells (IECs), and SAA potentiates the production of IL- 1β and IL- 23 in CX3CR1+ phagocytes, two cytokines that synergistically promote the production of IL- 22 in ILC3.”
• The Microbiome in Infectious Disease and Inflammation (2012, positive): “In contrast, mice deficient in both Myd88 and Trif have normal numbers of LP Th17 cells in the small and large intestines (151, 152).”
• Homeostatic immunity and the microbiota (2017, neutral): “…to most commensals that reside outside of the “demilitarized zone”, SFB interacts closely with the mucosal tissue via tight adhesion to Peyer’s Patches and epithelial cells, inducing cytoskeletal reorganization in these cells at the site of contact (Ivanov et al., 2008; Sczesnak et al., 2011).”
• Antibiotic-Induced Changes in the Intestinal Microbiota and Disease. (2016, background): “Indeed, Th17 differentiation in the small intestine (SI) LP depends on the microbiota; GF mice have a reduced Th17 compartment that is restored by introduction of fecal material from conventional mice [29].”