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Competitive Homing Assays to Study Gut-tropic T Cell Migration
Published on: March 2, 2011
Intestinal mast cell progenitors require CD49dbeta7 (alpha4beta7 integrin) for tissue-specific homing
M F Gurish1, H Tao, J P Abonia
1Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. mgurish@rics.bwh.harvard.edu
The Journal of Experimental Medicine
|November 7, 2001
Summary
The alpha4beta7 integrin is critical for mast cell progenitor (MCp) homing to the small intestine, but not the lungs. This molecule directs MCp migration from bone marrow to the gut for immune responses.
Area of Science:
- Immunology
- Cell Biology
- Gastroenterology
Background:
- Mast cells (MCs) are key players in allergic airway inflammation and intestinal immune responses to helminths.
- Mast cell progenitors (MCp) originate from bone marrow (BM) and mature into tissue-specific MCs.
- Mechanisms of MCp homing to peripheral tissues remain largely uncharacterized.
Purpose of the Study:
- To investigate the molecular mechanisms governing mast cell progenitor (MCp) homing to the small intestine.
- To identify specific homing molecules critical for MCp migration and tissue localization.
Main Methods:
- Limiting dilution analysis was used to quantify MCp concentrations in various tissues of genetically modified mice.
- Mice deficient in candidate homing molecules (e.g., beta7 integrin, alphaE integrin, beta2 integrin) were studied.
- Monoclonal antibodies targeting specific integrins and adhesion molecules were administered to assess their impact on MCp recovery after BM reconstitution.
Main Results:
- Beta7 integrin deficiency led to a near-complete absence of MCp in the small intestine, indicating its critical role in homing.
- Alpha4beta7 integrin, but not alphaEbeta7 integrin, was identified as the crucial molecule for MCp homing to the small intestine.
- Administration of anti-alpha4beta7 integrin, anti-alpha4 integrin, anti-beta7 integrin, or anti-MAdCAM-1 antibodies blocked MCp recovery in the small intestine.
- MCp were preserved in the lungs of beta7 integrin-deficient mice, suggesting tissue-specific homing mechanisms.
Conclusions:
- Alpha4beta7 integrin is essential for the specific extravasation and localization of mast cell progenitors in the small intestine.
- MCp migration to the small intestine involves a process originating in the bone marrow, followed by circulation and subsequent translocation into the intestine.
- Lymphocytes and natural killer cells do not play a significant role in directing MCp migration under basal conditions.
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