Gut CD103+ dendritic cells express indoleamine 2,3-dioxygenase which influences T regulatory/T effector cell balance and oral tolerance induction

Matteoli, Gianluca; Mazzini, Elisa; Iliev, Iliyan D.; Mileti, Erika; Fallarino, Francesca; Puccetti, Paolo; Chieppa, Marcello; Rescigno, María

doi:10.1136/gut.2009.185108

Cited by 328 publications

(286 citation statements)

References 42 publications

Supporting

Mentioning

264

Contrasting

Unclassified

Order By: Relevance

“…Some studies have noted that colonic IDO appears to be expressed largely in the epithelium (10), whereas other studies indicated that IDO is mainly expressed in local dendritic cells in the intestinal lamina propria (6). In this study, we showed that Ido1 mRNA was expressed at similar levels in the colonic epithelial and interstitial tissues of untreated wild-type mice, supporting the earlier findings that colonic epithelium expresses IDO under physiological conditions (10).…”

Section: Discussionsupporting

confidence: 89%

See 1 more Smart Citation

IDO1 Plays an Immunosuppressive Role in 2,4,6-Trinitrobenzene Sulfate–Induced Colitis in Mice

Takamatsu

Hirata

Ohtaki

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

IDO, an enzyme that degrades the essential amino acid l-tryptophan to N-formylkynurenine, is known to exert immunomodulatory effects in a number of diseases and disorders. IDO expression is increased in tumors, where it is thought to be involved in tumor evasion by suppressing the immune response. A competitive inhibitor of IDO is currently being tested in clinical trials for relapsed or refractory solid tumors; however, there remains a concern that attenuation of the immunosuppressive function of IDO might exacerbate inflammatory responses. In this study, we investigated the role of IDO in 2,4,6-trinitrobenzene sulfate (TNBS)–induced colitis in mice by gene deletion and pharmacological inhibition. TNBS treatment induced significantly more severe colitis in Ido1 gene–deficient (Ido1−/−) mice than in Ido1 wild-type (Ido1+/+) mice, indicating a role for IDO1 in suppression of acute colitis. Consistent with this, the expression of Ido1 was increased in the colonic interstitial tissues of TNBS-treated Ido1+/+ mice. Furthermore, transplantation of Ido1+/+ bone marrow cells into Ido1−/− mice reduced the pathological damage associated with colitis, altered the expression of cytokines, including IFN-γ, TNF-α, and IL-10, and increased the number of CD4+ Foxp3+ regulatory T cells in the colon. Pharmacological inhibition of IDO enzymatic activity by oral administration of 1-methyltryptophan (1-methyl-l-tryptophan or 1-methyl-d-tryptophan) significantly increased the severity of TNBS-induced colitis in mice, demonstrating that both stereoisomers can promote colitis. Collectively, our data indicate that IDO1 plays an important immunoregulatory role in the colon.

show abstract

Section: Discussionsupporting

confidence: 89%

“…In addition, recent studies have shown that increase of IDO concentrations in tissue inhibits migration of inflammatory cells, especially T cells (5). IDO is expressed in tissue macrophages and dendritic cells in a range of organs (6). Two types of IDO are known: IDO1 and the recently identified paralogue, IDO2 (7).…”

mentioning

confidence: 99%

IDO1 Plays an Immunosuppressive Role in 2,4,6-Trinitrobenzene Sulfate–Induced Colitis in Mice

Takamatsu

Hirata

Ohtaki

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…S6 A-E). Expression of indoleamine 2, 3-dioxygenase (IDO) in several regulatory DCs inhibits T-cell responses (6,20). However, T-cell proliferation was not increased by addition of an IDO inhibitor (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…CD103 + CX 3 CR1 − CD11b − DCs have been shown to generate and activate gut-tropic CD8 + T cells (16,17). These DCs have further been shown to induce development of Foxp3 + T reg cells (18)(19)(20). CX 3 CR1 + CD11b + DCs have been shown to mediate inflammatory responses through the induction of Th1 and Th17 cell development (15,(21)(22)(23)(24).…”

mentioning

confidence: 99%

Intestinal CX ₃ C chemokine receptor 1 ^high (CX ₃ CR1 ^high ) myeloid cells prevent T-cell-dependent colitis

Kayama

Ueda

Sawa

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Adequate activation of CD4 + T lymphocytes is essential for host defense against invading pathogens; however, exaggerated activity of effector CD4 + T cells induces tissue damage, leading to inflammatory disorders such as inflammatory bowel diseases. Several unique subsets of intestinal innate immune cells have been identified. However, the direct involvement of innate immune cell subsets in the suppression of T-cell-dependent intestinal inflammation is poorly understood. Here, we report that intestinal CX 3 C chemokine receptor 1 high (CX 3 CR1 high ) CD11b + CD11c + cells are responsible for prevention of intestinal inflammation through inhibition of T-cell responses. These cells inhibit CD4 + T-cell proliferation in a cell contact-dependent manner and prevent T-cell-dependent colitis. The suppressive activity is abrogated in the absence of the IL-10/Stat3 pathway. These cells inhibit T-cell proliferation by two steps. Initially, CX 3 CR1 high CD11b + CD11c + cells preferentially interact with T cells through highly expressed intercellular adhesion molecule-1/vascular cell adhesion molecule-1; then, they fail to activate T cells because of defective expression of CD80/CD86. The IL-10/Stat3 pathway mediates the reduction of CD80/CD86 expression. Transfer of wild-type CX 3 CR1 high CD11b + CD11c + cells prevents development of colitis in myeloid-specific Stat3-deficient mice. Thus, these cells are regulatory myeloid cells that are responsible for maintaining intestinal homeostasis. mucosal immunology | innate immunity

show abstract

“…However, it is important to remember that the data concerning migratory CD103 + cells have been derived in mice and we do not know about the situation in humans. However, it has been shown that CD103 + CD11c + HLADR + cells derived from human colon express Indoleamine 2,3-dioxygenase, which in mice is involved in the ability of CD103 + DCs to drive Foxp3 + Treg cell development [36]. This suggests similarity between CD103 + DCs in mice and humans.…”

Section: Phagocyte Subsets In the Human Intestinementioning

confidence: 93%

Intestinal dendritic cell and macrophage subsets: Tipping the balance to Crohn's Disease?

Magnusson

Wick

2011

European Journal of Microbiology and Immunology

View full text Add to dashboard Cite

Gut CD103+ dendritic cells express indoleamine 2,3-dioxygenase which influences T regulatory/T effector cell balance and oral tolerance induction

Abstract: We identified a new IDO-dependent pathway leading to acquisition of tolerogenic functions in mucosal CD103-expressing DCs, indicating IDO as a possible therapeutic target for gut disorders.

Cited by 328 publications

References 42 publications

IDO1 Plays an Immunosuppressive Role in 2,4,6-Trinitrobenzene Sulfate–Induced Colitis in Mice

IDO1 Plays an Immunosuppressive Role in 2,4,6-Trinitrobenzene Sulfate–Induced Colitis in Mice

Intestinal CX ₃ C chemokine receptor 1 ^high (CX ₃ CR1 ^high ) myeloid cells prevent T-cell-dependent colitis

Intestinal dendritic cell and macrophage subsets: Tipping the balance to Crohn's Disease?

Contact Info

Product

Resources

About

Gut CD103+ dendritic cells express indoleamine 2,3-dioxygenase which influences T regulatory/T effector cell balance and oral tolerance induction

Abstract: We identified a new IDO-dependent pathway leading to acquisition of tolerogenic functions in mucosal CD103-expressing DCs, indicating IDO as a possible therapeutic target for gut disorders.

Cited by 328 publications

References 42 publications

IDO1 Plays an Immunosuppressive Role in 2,4,6-Trinitrobenzene Sulfate–Induced Colitis in Mice

IDO1 Plays an Immunosuppressive Role in 2,4,6-Trinitrobenzene Sulfate–Induced Colitis in Mice

Intestinal CX 3 C chemokine receptor 1 high (CX 3 CR1 high ) myeloid cells prevent T-cell-dependent colitis

Intestinal dendritic cell and macrophage subsets: Tipping the balance to Crohn's Disease?

Contact Info

Product

Resources

About

Intestinal CX ₃ C chemokine receptor 1 ^high (CX ₃ CR1 ^high ) myeloid cells prevent T-cell-dependent colitis