CXCL10-producing mucosal CD4+ T cells, NK cells, and NKT cells are associated with chronic colitis in IL-10-/- mice, which can be abrogated by anti-CXCL10 antibody inhibition

Udai P. Singh, Shailesh Singh, Rajesh Singh, Yingzi Cong, Dennis D. Taub, James W. Lillard

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

We have shown previously that there is a temporal increase in the levels of CXCL10 and CXCR3 mRNA during spontaneous murine colitis. We now show that CXCL10 is significantly expressed by mucosal CD4+ T cells, natural killer (NK) cells, and NKT cells, but not by dendritic cells (DCs), during chronic murine colitis. CXCL10 blockade alleviated chronic colitis and attenuated the associated increase in serum amyloid A (SAA), interleukin-12 (IL-12)p40, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-1α, and IL-1β levels as well as in the number of CD4+ T, NKT, and NK cells that express CXCL10 and CXCR3, compared with groups treated with control antibody (Ab). After CXCL10 blockade, the number of CXCR3+ DCs in the mesenteric lymph nodes (MLNs) and Peyer's patches (PPs) were increased to levels found before the onset of colitis. In contrast, the numbers of splenic and intestinal lamina propria (LP) CXCR3 + DCs were reduced after anti-CXCL10 Ab treatment, compared with controls. Ex vivo antigen and CXCL10 stimulation of mucosal cells caused an increase in MHC class II, CD40, and CD86 as well as a decrease in CD30 ligand (CD30L) expression by DCs. This study provides insights into CXCL10 expression during inflammatory bowel disease (IBD) and the cellular and molecular mechanisms of CXCL10-mediated colitis. Our data also support the premise that CXCL10 blockade can attenuate chronic colitis by preventing the activation and recruitment of CXCR3+ leukocytes during IBD.

Original languageEnglish (US)
Pages (from-to)31-43
Number of pages13
JournalJournal of Interferon and Cytokine Research
Volume28
Issue number1
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

Fingerprint

Natural Killer T-Cells
Colitis
Natural Killer Cells
Interleukin-10
Anti-Idiotypic Antibodies
T-Lymphocytes
Dendritic Cells
Interleukin-1
Inflammatory Bowel Diseases
CD30 Ligand
Serum Amyloid A Protein
Peyer's Patches
Interleukin-12
Interferons
Mucous Membrane
Leukocytes
Tumor Necrosis Factor-alpha
Lymph Nodes
Antigens
Messenger RNA

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Cell Biology

Cite this

CXCL10-producing mucosal CD4+ T cells, NK cells, and NKT cells are associated with chronic colitis in IL-10-/- mice, which can be abrogated by anti-CXCL10 antibody inhibition. / Singh, Udai P.; Singh, Shailesh; Singh, Rajesh; Cong, Yingzi; Taub, Dennis D.; Lillard, James W.

In: Journal of Interferon and Cytokine Research, Vol. 28, No. 1, 01.01.2008, p. 31-43.

Research output: Contribution to journalArticle

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