Mucosal Immunity includes many molecular entities, many of which remain poorly understood. We have used gene array analyses to identify three chemokines (CXCL14, CXCL17 and CCL28) that exhibit very high expression in human mucosal tissues. Only these three chemokines (out of 48 known human ligands) exhibit this close association with mucosal tissues. These chemokines likely represent some of the most abundant proteins present, for example, in human saliva, yet we know very little about them. Furthermore, their role in mucosal immunity is virtually unexplored. We therefore aim to study these 'mucosal'chemokines.
In Specific aim 1, we will map the cells that produce these chemokines in the various mucosal tissues (oral cavity, bronchus, trachea, esophagus, gut and the female reproductive tract) by immunohistochemistry and/or in situ hybridization. These results will point to future experiments aimed at evaluating in greater detail the role of these chemokines in mucosal immunity.
In Specific aim 2, we will test the hypothesis that these chemokines have microbicidal activity. We will test several microorganisms, including gram (+), gram (-), Candida albicans and Chlamydia trachomatis. If confirmed, this result would indicate that these chemokines may be major players in maintaining the balance between the mucosa of human body cavities and normal or pathogenic flora present in these sites. For example, these chemokines may play major roles in diseases such as periodontal disease, or vaginal candidiasis. Finally, we have observed that one of these chemokines, CXCL14, is specifically expressed in taste buds but not in lingual epithelium. We will analyze the taste buds of CXCL14 knockout mice using various biomarkers of taste bud cells (those that mediate sweet, bitter, umami and sour taste perception as well as precursor taste cells). These experiments will indicate whether the taste buds of CXCL14-/- mice exhibit any alterations and may point to a role for CXCL14 in taste bud development. Taken together, these experiments should provide us with a new understanding of the functions of these chemokines in mucosal tissues. This project aims to characterize three chemokines (CXCL14, CXCL17, CCL28) that are highly expressed in mucosal tissues including those in various human body cavities (oral cavity, vagina, etc). It will explore several potential functions of these chemokines including microbicidal activity as well as a potential role of CXCL14 in taste bud development.
This project aims to characterize three chemokines (CXCL14, CXCL17, CCL28) that are highly expressed in mucosal tissues including those in various human body cavities (oral cavity, vagina, etc). It will explore several potential functions of these chemokines including microbicidal activity as well as a potential role of CXCL14 in taste bud development.
| Burkhardt, Amanda M; Tai, Kenneth P; Flores-Guiterrez, Juan P et al. (2012) CXCL17 is a mucosal chemokine elevated in idiopathic pulmonary fibrosis that exhibits broad antimicrobial activity. J Immunol 188:6399-406 |
| Zlotnik, Albert; Yoshie, Osamu (2012) The chemokine superfamily revisited. Immunity 36:705-16 |
| Zlotnik, Albert; Burkhardt, Amanda M; Homey, Bernhard (2011) Homeostatic chemokine receptors and organ-specific metastasis. Nat Rev Immunol 11:597-606 |
