Janus kinase inhibitors vs. abatacept about safety and efficacy for patients with rheumatoid arthritis-associated interstitial lung disease: a retrospective nested case-control study.

Background: Interstitial lung disease (ILD) related to rheumatoid arthritis (RA) is among the leading causes of death and an essential prognostic factor. There is only limited evidence for the safety of anti-rheumatic drugs for patients with RA-ILD. The aim of this study is to investigate the safety and efficacy of Janus kinase inhibitors (JAKis) by comparing it with abatacept (ABT) in patients with RA-ILD.

A large increase of sour taste receptor cells in Skn-1-deficient mice does not alter the number of their sour taste signal-transmitting gustatory neurons.

The connections between taste receptor cells (TRCs) and innervating gustatory neurons are formed in a mutually dependent manner during development. To investigate whether a change in the ratio of cell types that compose taste buds influences the number of innervating gustatory neurons, we analyzed the proportion of gustatory neurons that transmit sour taste signals in adult Skn-1a mice in which the number of sour TRCs is greatly increased. We generated polycystic kidney disease 1 like 3-wheat germ agglutinin (pkd1l3-WGA)/Skn-1a and pkd1l3-WGA/Skn-1a mice by crossing Skn-1a mice and pkd1l3-WGA transgenic mice, in which neural pathways of sour taste signals can be visualized.

Expression of serotonin receptor genes in cranial ganglia.

Taste cells release neurotransmitters to gustatory neurons to transmit chemical information they received. Sweet, umami, and bitter taste cells use ATP as a neurotransmitter. However, ATP release from sour taste cells has not been observed so far.

Oral and extra-oral taste perception.

Of the five basic taste qualities, the molecular mechanisms underlying sweet, bitter, and umami (savory) taste perception have been extensively elucidated, including the taste receptors and downstream signal transduction molecules. Recent studies have revealed that these taste-related molecules play important roles not only in the oral cavity but also in a variety of tissues including the respiratory tract, stomach, intestines, pancreas, liver, kidney, testes, and brain. This review covers the current knowledge regarding the physiological roles of taste-related molecules in the oral and extra-oral tissues.

Genetic tracing of the gustatory neural pathway originating from Pkd1l3-expressing type III taste cells in circumvallate and foliate papillae.

Polycystic kidney disease 1-like 3 (Pkd1l3) is expressed specifically in sour-sensing type III taste cells that have synaptic contacts with afferent nerve fibers in circumvallate (CvP) and foliate papillae (FoP) located in the posterior region of the tongue, although not in fungiform papillae (FuP) or the palate. To visualize the gustatory neural pathways that originate from type III taste cells in CvP and FoP, we established transgenic mouse lines that express the transneuronal tracer wheat germ agglutinin (WGA) under the control of the mouse Pkd1l3 gene promoter/enhancer. The WGA transgene was accurately expressed in Pkd1l3-expressing type III taste cells in CvP and FoP.

Interaction between PKD1L3 and PKD2L1 through their transmembrane domains is required for localization of PKD2L1 at taste pores in taste cells of circumvallate and foliate papillae.

The polycystic kidney disease 1-like 3 (PKD1L3) and polycystic kidney disease 2-like 1 (PKD2L1) proteins have been proposed to form heteromers that function as sour taste receptors in mammals. Here, we show that PKD1L3 and PKD2L1 interact through their transmembrane domains, and not through the coiled-coil domain, by coimmunoprecipitation experiments using a series of deletion mutants. Deletion mutants lacking the critical interaction region were not transported to the cell surface and remained in the cytoplasm, whereas PKD1L3 and PKD2L1 proteins were expressed at the cell surface when both are transfected.