The expression and regulation of amphiregulin on human basophils and CD4 T cells (36.16)

• Published in: The Journal of immunology (1950) 2009-04, Vol.182 (1_Supplement), p.36-36.16
• Main Authors: Qi, Yilin, Operario, Darwin J., Oberholzer, Chris M., Kobie, James J., Mosmann, Tim R.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.182.Supp.36.16

Amphiregulin (AR), a member of the Epidermal Growth Factor family, is expressed during some allergic (type 2) responses by activated mouse Th2 cells, or human mast cells. AR produced by mouse hematopoietic cells contributes to the elimination of a nematode infection by a Type 2 effector response. We therefore tested whether human peripheral blood mononuclear cells produced AR in response to T cell activation. Unexpectedly, the expression of AR mRNA and protein was found in a non-T cell population. The AR-producing cells were basophils, as judged by histological staining and expression of CD203c and CD123 (the IL-3 receptor alpha chain). AR expression by basophils in response to anti-TCR stimulation required IL-3 produced by T cells, and IL-3 alone induced high levels of AR expression by purified basophils. Mouse basophils also produced AR upon activation. Although human CD4 T cells stimulated through the TCR alone did not express AR, we found that a combination of TCR stimulation and intracellular cAMP upregulation induced human CD4 cells (particularly Th2 cells) to express AR. In contrast, most other cytokines were downregulated by elevated cAMP levels. AR expressed by human basophils, mast cells and CD4 T cells may contribute to tissue remodeling during type 2 immune responses such as asthma. Supported by a Sandler Program in Asthma Research grant to TRM.