Anti-IL9 monoclonal antibody Made to order

We have previously shown that expression of a Ca2+-activated Cl- channel (mCLCA3 in mice and hCLCA1 in humans) is up-regulated along with goblet cell metaplasia and mucus overproduction in the lungs of interleukin 9 (IL9) transgenic mice, and in human primary lung cultures by IL4, IL13 and IL9. We show here that hCLCA1 expression in NCI-H292 cells specifically induces soluble gel-forming mucin production. Moreover, niflumic acid (NFA), a blocker of hCLCA1-dependent Cl- efflux, inhibits MUC5A/C production in these cells. NFA treatment during natural antigen-exposure, where mCLCA3 is greatly up-regulated in the lung, significantly reduces airway inflammation, goblet cell metaplasia and mucus overproduction in vivo. These data suggest that this Ca2+-activated Cl- channel plays an important role in epithelial-regulated inflammatory responses, including goblet cell metaplasia, and represents a potential novel therapeutic target for the control of mucus overproduction in chronic pulmonary disorders.

IL-9 was first described in the late 1980s as a member of a growing number of cytokines that had pleiotropic functions in the immune system. Although many biological functions have been attributed to IL-9, it remains an understudied cytokine. A resurgence of interest in IL-9 has been spurred by recent work demonstrating a role for IL-9 in regulating inflammatory immunity and defining the transcription factors that activate the Il9 gene in cells that most efficiently produce IL-9. In this review, we summarize the characterization of IL-9 biological activities, highlight roles for the cytokine that are clearly defined, and outline questions regarding IL-9 functions that still require further exploration. The Journal of Immunology, 2011, 186: 3283-3288.