IL-2Rβ-dependent signaling and CD103 functionally cooperate to maintain tolerance in the gut mucosa

Xiaomei Yuan, Michael J. Dee, Norman H. Altman, Thomas Malek

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

A network of mechanisms operates to maintain tolerance in the gut mucosa. Although CD103 marks many lymphoid cells within the gut, its direct functional role in intestinal tolerance is poorly understood. CD103 may be part of a redundant pathway, as CD103-/- mice do not exhibit autoimmunity. To reduce such redundancy, CD103-/- mice were crossed to mice (designated Y3) whose T cells expressed a mutant IL-2Rβ-chain that lowers IL-2R signaling. Unlike overtly healthy Y3 mice, all Y3/CD103-/- mice rapidly developed severe colitis. The large intestine of these mice contained an increase in CD4+ Th1 and Th17 effector cells and a reduced ratio of regulatory T cells (Tregs). Importantly, colitis was effectively prevented by the transfer of wild-type Tregs into Y3/CD103-/- mice. Impaired intestinal tolerance was not attributed to an obvious lack of CD103-dependent gene regulation or intestinal homing/retention by Tregs nor a lack of functional activities typically associated with CD103+ dendritic cells, such as peripherally induced Treg development or imprinting CCR9 and α4β7 homing molecules on Tregs and T effector cells. Transcriptome analysis of Tregs was consistent with altered homeostasis due to impaired IL-2Rβ-dependent signaling with minimal dysregulation added by the absence of CD103. Rather, the absence of CD103 functioned to alter the localization of the cells within the gut microenvironment that may alter Treg homeostasis. Thus, IL-2Rβ-dependent signaling and CD103 normally cooperate through distinctive processes to promote Treg homeostasis and immune tolerance.

Original languageEnglish
Pages (from-to)1334-1346
Number of pages13
JournalJournal of Immunology
Volume194
Issue number3
DOIs
StatePublished - Jan 1 2015

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Mucous Membrane
Homeostasis
Colitis
Th17 Cells
Immune Tolerance
Large Intestine
Gene Expression Profiling
Regulatory T-Lymphocytes
Autoimmunity
Dendritic Cells
Lymphocytes
T-Lymphocytes
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

IL-2Rβ-dependent signaling and CD103 functionally cooperate to maintain tolerance in the gut mucosa. / Yuan, Xiaomei; Dee, Michael J.; Altman, Norman H.; Malek, Thomas.

In: Journal of Immunology, Vol. 194, No. 3, 01.01.2015, p. 1334-1346.

Research output: Contribution to journalArticle

Yuan, Xiaomei ; Dee, Michael J. ; Altman, Norman H. ; Malek, Thomas. / IL-2Rβ-dependent signaling and CD103 functionally cooperate to maintain tolerance in the gut mucosa. In: Journal of Immunology. 2015 ; Vol. 194, No. 3. pp. 1334-1346.
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