Indeed, these autoantibodies bind to the extracellular loops of AQP5 and hamper water flux. and antigen cell presentation, thereby, in a vicious circle, amplify the interactions between epithelial cells and immune cells [7]. Furthermore, following interferon type 1 secretion, there is also secretion of B-cell activating factor by the activated epithelial cells, thereby promoting B-cells activation and proliferation [5,8]. These well-defined sequences of immune activation, leading to aberrant lymphocyte homing, unrestrained pro inflammatory cytokine production, and the corollary of SG disorganization and destruction, clearly delineate and promote the predominant role of the epithelial cells as key to the development of SS, hence the term [9,10]. The mechanisms responsible for salivary gland hypofunction and the corollary of xerostomia are not fully deciphered, but there is sufficient compelling evidence to substantiate the role of salivary gland destruction due to the autoimmune underpinnings TFMB-(R)-2-HG in SS as described above. Moreover, there are also several lines of proofs undergirding the fact that dry mouth and dry eyes do not solely result from gland destruction, and that other mechanisms, including the presence of anti-muscarinic autoantibodies, altered mucin expression, nitric oxide-mediated salivary gland dysfunction, and modified aquaporin-5 (AQP5) distribution are also potential active players responsible for the sicca syndrome. In this review, we describe the involvement of aquaporins (AQPs) in the pathogenic features of SS, focusing on salivary glands, and the potential diagnostic and therapeutic possibilities of AQPs in SS. 2. Expression and Function of AQPs in Salivary Glands AQPs, a family of water-permeable channels, are small transmembrane proteins of about 28 kDa, implicated in transcellular water permeability in all living organisms [11]. AQPs are made of six transmembrane helices and two short helices comprising each a canonical Asparagine-Proline-Alanine (NPA) motif (Figure 1A). The AQP monomers need to associate as tetramers to be functional [12] (Figure 1B). It is now well established that transcellular water fluxes occur through both diffusion and a facilitated pathway mediated by AQPs [12]. Water diffusion occurs at relatively low velocity and volume, while transcellular water movement through AQPs occurs at much higher TFMB-(R)-2-HG volumes to cross membranes at a much higher velocity. In most tissues, TFMB-(R)-2-HG AQPs-mediated water flow is directed by osmotic LAMNB2 gradients and osmosis. So far, 13 mammalian AQPs have been identified [13,14]. These AQPs are classified into three subfamilies according to their permeability features and sequences homologies. The subfamilies include: (a) the classical AQPs only permeable to water (AQP0, AQP1, AQP2, AQP4, AQP5, AQP6, and AQP8); (b) TFMB-(R)-2-HG the aquaglyceroporins permeable to water as well as to small uncharged molecules, such as glycerol and urea (AQP3, AQP7, AQP9, and AQP10), and (c) unorthodox AQPs, whose permeability still remains to be clearly established (AQP11 and AQP12) [12,13,14] (Figure 1C). Open in a separate window Figure 1 Characteristics and classification of AQPs. A: AQPs are made of six transmembrane helices and two short helices containing the NPA motifs for the classical AQPs and aquaglyceroporins, or NPC motifs for unorthodox AQPs. B: AQPs need to associate as tetramers to be functional. C: AQPs are subdivided into the classical AQPs, the aquaglyceroporins and the unorthodox AQPs. Of the known AQPs, six are expressed in mammalian SG [15]. AQP1 is.