23 explore mucosal adjuvants known for their capacity to directly or indirectly stimulate B-cell immunity and Ig production. TSLP, but R428 datasheet not APRIL nor BAFF, induced strong and sustained serum and mucosal immune responses after nasal immunization, comparable to those seen with cholera toxin, a natural mucosal adjuvant. Intranasal, but not intradermal,

immunization-induced vaginal IgA responses. As expected, TSLP shifted the immune response towards a Th2-cell type response. On this basis, the authors suggest that TSLP may be a promising mucosal adjuvant with a very specific effector profile. The data of Van Roey et al. 23 open up several perspectives for the design of mucosal adjuvants. Interestingly, the properties evidenced for TSLP are not shared by the other cytokines currently used as adjuvants (Fig. 1). Thus extending the portfolio of complementary functional profiles to match a diversity of therapeutic needs depending on the physiopathological context. The data also suggest that

TSLP is Estrogen antagonist a recombinant adjuvant that seems to induce stronger immune responses than current natural mucosal adjuvants, such as cholera toxin. Thus, TSLP may be considered for inclusion in current mucosal vaccines to further enhance their intrinsic adjuvant potential. Despite the promising data of Van Roey et al. 23, several questions remain. First, extrapolation to the human setting needs caution because of species-specific differences between mouse and human TSLP 19. Secondly,

the potential toxicity of intranasal injection of TSLP needs to be considered, given its pro-allergic effects. Finally, in common with all cytokines, TSLP displays cellular and functional pleiotropy. Besides promoting inflammatory Th2-cell responses, TSLP can induce Treg-cell development in the thymus 25, and at low Anacetrapib dose in the intestine 26. In the HIV setting, epithelial-derived TSLP can enhance DC-mediated infection of CD4+ T cells and virus spreading 27. Therefore, follow-up studies will be important to validate the effect of TSLP on mucosal immunity and to precisely define the underlying mechanisms, as well as the potential of TSLP-activated DCs to imprint T cells with mucosa-homing potential. Pre-clinical studies should include a dose-response evaluation of the adjuvant effects, together with toxicity studies and careful immune monitoring should help to evaluate the balance of Teff versus Treg-cell induction by TSLP in relevant settings. If the balance favors effector responses with a good safety profile, TSLP may prove to be an interesting new player in the portfolio of vaccine adjuvants and immune modifiers. The author thanks Olivier Lantz for helpful suggestions, and Fabienne Fossard for help with the figure preparation. Conflict of interest: The authors have declared no conflict of interest. See accompanying article: http://dx.doi.org/10.1002/eji.