IL-33 is a proinflammatory cytokine that plays a pivotal role in allergic disorders. In a transgenic mouse expressing IL-33 driven by a keratin-14 promoter (IL33tg), atopic dermatitis (AD)-like inflammation develops spontaneously with the activation of group 2 innate lymphoid cells (ILC2s). However, it remains unknown how effector cells, such as T helper type 2 cells, ILC2s, and basophils, contribute to the inflammatory process induced by IL-33. To address the question, we examined the phenotype of IL33tg mice lacking each of these cells. AD-like inflammation still developed in Rag2KO IL33tg mice lacking T and B cells; in contrast, when ILC2s were depleted in IL33tg mice via bone marrow transplantation from ILC2-lacking, RAR-related orphan receptor alphaedeficient mice, the development of AD-like inflammation was almost completely suppressed. Basophils were accumulated in the inflamed skin of IL33tg mice, and AD-like inflammation was alleviated by the conditional depletion of basophils using anti-FcεRIa antibodies or a Bas-TRECK transgenic mouse system. In these basophil-depleted IL33tg skins, ILC2s were decreased, and cytokines and chemokines such as IL-5, IL-13, and CCL5 were reduced. From these results, we suggest that IL-33einduced AD-like inflammation is dependent on innate immune responses that are mediated by ILC2s in concert with basophils.

Group 2 innate lymphoid cells (ILCs) are thought to contribute to the pathogenesis of atopic dermatitis (AD). IL-4 stimulates T helper type 2 (Th2) cells and ILC2s to proliferate and produce cytokines. Dupilumab, an antibody against the IL-4 receptor, is used in AD therapy. We speculated that its efficacy might involve blocking the activation of Th2 cells and ILC2s via IL-4. Here, we examined circulating Th2 cells and ILC2s in 27 Japanese patients with AD before and after the administration of dupilumab. Between 0 and 4 months after dupilumab administration, the percentages of Th2 cells and ILC2s were decreased. Notably, ILC2/3 ratio was decreased after dupilumab treatment. Interestingly, ILC2/3 ratio before dupilumab treatment were significantly higher in high responders than in low responders to dupilumab. To resolve the molecular signatures of the Th2 and ILC2s in AD, we sorted CD4 + T cells and ILCs from peripheral blood and analyzed their transcriptomes using the BD Rhapsody Single-cell RNA sequencing system. Between 0 and 4 months after dupilumab administration, the Th2 and ILC2 cluster gene signatures were downregulated. Thus, dupilumab might improve dermatitis by suppressing the Th2 cell and ILC2 populations and altering the Th2 and ILC2 repertoire in patients with AD.

Dupilumab was effective for 53 patients with moderate‐to‐severe AD in our daily practice. TARC reduction, however, did not necessarily reflect improved AD.

The most important side effect of pirfenidone is photosensitivity caused by the phototoxic effect. Here, we report a rare case of photosensitive drug eruption due to a photoallergic reaction, which was proven through a photopatch test and DLST.

Patients with generalized pustular psoriasis (GPP) often present with symptoms that must be differentiated from sepsis. Procalcitonin (PCT) and presepsin (P-SEP) are widely used as biomarkers for sepsis; therefore, we examined the serum PCT and P-SEP levels in patients with psoriatic diseases. The enrolled patients included 27 with psoriasis vulgaris (PV) (22 males, 5 females; mean age 47.7 years), 12 with psoriatic arthritis (PsA) (8 males, 4 females; mean age 51.3 years), and 15 with GPP (10 males, 5 females; mean age 63.7 years). The mean serum PCT levels in patients with PV, PsA, and GPP were 0.01 ng/mL (25th–75th percentile; 0.00–0.03), 0.013 ng/mL (0.00–0.03), and 0.12 ng/mL (0.05–0.18), respectively; the levels of PCT were higher for patients with GPP than with PV or PsA but were lower than the PCT cutoff value (0.5 ng/mL) for the diagnosis of infection. The mean serum P-SEP levels in patients with PV, PsA, and GPP were 144.9 pg/mL (25th–75th percentile; 78–181), 168.1 pg/mL (124–203), and 479.9 pg/mL (216–581), respectively. Unexpectedly, the levels of P-SEP in the patients with GPP were as high as the P-SEP cutoff value (317 to 647 pg/mL) used for the diagnosis of infection. We also found that neutrophils produced P-SEP, suggesting that the high serum P-SEP levels in patients with GPP might arise at least in part due to the P-SEP derived from neutrophils activated in GPP. Both serum PCT and P-SEP might therefore be useful as novel serum biomarkers for GPP because their levels were decreased by GPP treatments. However, the measurement of PCT might be more useful than the measurement of P-SEP for discriminating between GPP and sepsis.

No abstract

No abstract

No abstract