Psoriatic arthritis (PsA) is a chronic inflammatory arthritis of unknown etiology, and currently the cellular and molecular interactions that dictate its pathogenesis remain elusive. A role of the interleukin-23 (IL-23)/IL-23R (IL-23 receptor) interaction in the development of psoriasis and PsA is well established. As IL-23 regulates the differentiation and activation of innate and adaptive immunity, it pertains to a very complex pathophysiology involving a plethora of effectors and transducers. In this review, we will discuss recent advances on the cellular and molecular pathophysiological mechanisms that regulate the initiation and progression of PsA as well as new therapeutic approaches for IL-23/IL-23R targeted therapeutics.

Interleukin-23 (IL-23), an IL-12 family cytokine, plays pivotal roles in pro-inflammatory T helper 17 cell responses linked to autoimmune and inflammatory diseases. Despite intense therapeutic targeting, structural and mechanistic insights into receptor complexes mediated by IL-23, and by IL-12 family members in general, have remained elusive. We determined a crystal structure of human IL-23 in complex with its cognate receptor, IL-23R, and revealed that IL-23R bound to IL-23 exclusively via its N-terminal immunoglobulin domain. The structural and functional hotspot of this interaction partially restructured the helical IL-23p19 subunit of IL-23 and restrained its IL-12p40 subunit to cooperatively bind the shared receptor IL-12Rβ1 with high affinity. Together with structural insights from the interaction of IL-23 with the inhibitory antibody briakinumab and by leveraging additional IL-23:antibody complexes, we propose a mechanistic paradigm for IL-23 and IL-12 whereby cognate receptor binding to the helical cytokine subunits primes recruitment of the shared receptors via the IL-12p40 subunit.

We have observed the decays B--> phiK and phiK(*) in a sample of over 45 million B mesons collected with the BABAR detector at the PEP-II collider. The measured branching fractions are B(B+--> phiK+) = (7.7(+1.6)(-1.4)+/-0.8)x10(-6), B(B0--> phiK0) = (8.1(+3.1)(-2.5)+/-0.8)x10(-6), B(B+--> phiK(*+)) = (9.7(+4.2)(-3.4)+/-1.7)x10(-6), and B(B0--> phiK(*0)) = (8.7(+2.5)(-2.1)+/-1.1)x10(-6). We also report the upper limit B(B+--> phipi(+))<1.4x10(-6) ( 90% C.L.).

We search for direct CP violation in charmless hadronic B decays observed in a sample of about 22.7 million B B̄ pairs collected with the BABAR detector at the SLAC PEP-II asymmetric-energy e+e- collider. We measure the following charge asymmetries: ACp(B ±→η′K±=-0.11±0. 11±0.02, ACP(B±→ωπ ±) = -0.01 -0.31+0.29±0.03, ACPB±→φK±)= -0.05±0.20±0.03, ACP(B± → φK*±)= -0.430.30+0.36±0.06, and ACP(B0→φ K*0)=0.00±0.27±0.03. © 2002 The American Physical Society.

The production of J/psi mesons in continuum e(+)e(-) annihilations has been studied with the BABAR detector at energies near the Upsilon(4S) resonance. The mesons are distinguished from J/psi production in B decays through their center-of-mass momentum and energy. We measure the cross section e(+)e(-)-->J/psi X to be 2.52+/-0.21+/-0.21 pb. We set a 90% C.L. upper limit on the branching fraction for direct Upsilon(4S)-->J/psi X decays at 4.7 x 10(-4).

We report a study of the B meson decays, B+ --> J/psiphiK+, B0 --> J/psiphiK(0)(S), B0 --> J/psiphi, B0 --> J/psieta, and B0 --> J/psieta' using 56 x 10(6) B(-)B events collected at the Upsilon(4S) resonance with the BABAR detector at the PEP-II e(+)e(-) asymmetric-energy storage ring. We measure the branching fractions B(B+ --> J/psiphiK+)=(4.4+/-1.4(stat)+/-0.5(syst))x 10(-5) and B(B0 --> J/psiphiK(0)(S))=(5.1+/-1.9(stat)+/-0.5(syst))x 10(-5), and set upper limits at 90% confidence level for the branching fractions B(B0 --> J/psiphi)<9.2 x 10(-6), B(B0 --> J/psieta)<2.7 x 10(-5), and B(B0 --> J/psieta')<6.3 x 10(-5).

We present a measurement of time-dependent CP-violating asymmetries in neutral B meson decays collected with the BABAR detector at the PEP-II asymmetric-energy e + e - collider at the Stanford Linear Accelerator Center. The data sample consists of 29.7 fb -1 recorded at the Υ(4S) resonance and 3.9 fb -1 off resonance. One of the neutral B mesons, which are produced in pairs at the Υ(4S), is fully reconstructed in the CP decay modes J/ΨK S 0 , Ψ(2S)K S 0 , X c1 K S 0 , J/ΨK* 0 (K* 0 →K s 0 π 0 ) and J/ΨK L 0 , or in flavor-eigenstate modes involving D(*)π/ρ/a 1 and J/ΨK* 0 (K* 0 →K + π - ). The flavor of the other neutral B meson is tagged at the time of its decay, mainly with the charge of identified leptons and kaons. A neural network tagging algorithm is used to recover events without a clear lepton or kaon tag. The proper time elapsed between the decays is determined by measuring the distance between the decay vertices. Wrong-tag probabilities, the time-difference resolution function, and the B 0 -B̄ 0 oscillation frequency Δm d are measured with a sample of about 6350 fully-reconstructed B 0 decays in hadronic flavor-eigenstate modes. A maximum-likelihood fit to this flavor eigenstate sample finds Δm d =0.516±0.016(stat)±0.010(syst) ps -1 . The value of the asymmetry amplitude sin 2Β is determined from a simultaneous maximum-likelihood fit to the time-difference distribution of the flavor-eigenstate sample and about 642 tagged B 0 decays in the CP-eigenstate modes. We find sin 2Β=0.59 ±0.14(stat)±0.05(syst), demonstrating that CP violation exists in the neutral B meson system. We also determine the value of the CP violation parameter |λ|=0.93±0.09(stat)±0.03(syst), which is consistent with the expectation of |λ|=1 for no direct CP violation.

The branching fractions of the exclusive decays B0-->K(*0)gamma and B+-->K(*+)gamma are measured from a sample of (22.74+/-0.36)x10(6) BB decays collected with the BABAR detector at the PEP-II asymmetric e(+)e(-) collider. We find B (B0-->K(*0)gamma) = [4.23+/-0.40(stat)+/-0.22(syst)]x10(-5), B(B+-->K(*+)gamma) = [3.83+/-0.62(stat)+/-0.22(syst)]x10(-5) and constrain the CP-violating charge asymmetry to be -0.170K(*)gamma)<0.082 at 90% C.L.