TSLP directly impairs pulmonary Treg function: association with aberrant tolerogenic immunity in asthmatic airway
<p>Abstract</p> <p>Background</p> <p>Even though thymic stromal lymphopoietin (TSLP) has been implicated in the development of allergic inflammation, its influence on immune tolerance mediated by regulatory T cells (Treg) have not been explored. We aimed to dissect the...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-03-01
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| Series: | Allergy, Asthma & Clinical Immunology |
| Online Access: | http://www.aacijournal.com/content/6/1/4 |
| Summary: | <p>Abstract</p> <p>Background</p> <p>Even though thymic stromal lymphopoietin (TSLP) has been implicated in the development of allergic inflammation, its influence on immune tolerance mediated by regulatory T cells (Treg) have not been explored. We aimed to dissect the influence of TSLP on immunosuppressive activities of Treg and its potential consequences in human allergic asthma.</p> <p>Methods</p> <p><it>I</it><it>n vitro </it>culture system was utilized to study the effects of TSLP on human Treg. The functional competency of pulmonary Treg from a cohort of 15 allergic asthmatic, 15 healthy control, and 15 non-allergic asthmatic subjects was also evaluated by suppression assays and flow cytometric analysis.</p> <p>Results</p> <p>Activated pulmonary Treg expressed TSLP-R and responded to TSLP-mediated activation of STAT5. TSLP directly and selectively impaired IL-10 production of Treg and inhibited their suppressive activity. In human allergic asthma, pulmonary Treg exhibited a significant decrease in suppressive activity and IL-10 production compared to healthy control and non-allergic asthmatic counterparts. These functional alterations were associated with elevated TSLP expression in bronchoaveolar lavage fluid (BAL) of allergic asthmatic subjects. Furthermore, allergic asthmatic BAL could suppress IL-10 production by healthy control pulmonary Treg in a TSLP-dependent manner.</p> <p>Conclusions</p> <p>These results provide the first evidences for a direct role of TSLP in the regulation of suppressive activities of Treg. TSLP mediated inhibition of Treg function might present a novel pathologic mechanism to dampen tolerogenic immune responses in inflamed asthmatic airway.</p> |
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| ISSN: | 1710-1484 1710-1492 |