T follicular helper (T(FH)) cells are central to the development and regulation of T cell-dependent humoral immune responses. The transcriptional repressor BCL6 is required for T(FH) responses, but the kinetics of BCL6 protein expression in activated CD4(+) T cells have not been established. We measured BCL6 expression during T(FH) cell development at the single-cell level using intracellular staining and YFP-BCL6 fusion protein reporter mice. BCL6 was immediately upregulated in all dividing T cells during dendritic cell-T cell interactions. A second wave of early BCL6 expression coincided with the induction of CXCR5, resulting in a distinct and stable T(FH) cell population. Cognate B cells were not required for the induction of BCL6, but supported the expansion of T(FH) cells. These data suggest that BCL6 participates in very early events in T(FH) cell development, and that repeated encounters with APCs reinforce BCL6 expression, thereby establishing the T(FH) cell phenotype.
Background: The nature of itch sensation varies depending upon the patient and the disease. However, few studies have focused on verbal expressions describing itch of atopic dermatitis (AD) in quality. Objectives: To investigate itch quality in patients with AD compared with that of urticaria. Methods: We conducted an online questionnaire survey describing itch experiences in June 2021. Participants were Japanese patients who had visited hospitals for their consultations and treatments of AD or urticaria in the last 6 months, and 295 and 290 responses, respectively, to questions using 12 terms describing itch quality were analyzed. Results: The most suitable expression describing intense itch that patients could not help scratching differed between the diseases, where most AD patients selected “muzumuzu” (a mimetic word for creepy–crawly itch) (27%) or “painful itch” (20%), and most urticaria patients selected “muzumuzu” (24%) or “itch like mosquito bites” (22%). The most suitable expressions describing itch that would make patients happiest if improved was “painful itch” (27%) in AD patients, significantly higher than urticaria patients (19%). More AD patients (55%) responded that they sometimes felt itch even after the skin symptoms had subsided than urticaria patients (41%). The most suitable expression of remnant itch selected was “muzumuzu” for AD (58/161 patients, 36%) and urticaria (29/120 patients, 24%). Conclusion: The quality of itch sensations can be classified not only between diseases but also during the clinical course of each disease. Significant expressions that patients with AD use to describe itch sensations could promote more appropriate treatment for itch.
The tumor necrosis factor receptor superfamily member HVEM is one of the most frequently mutated surface proteins in germinal center (GC)-derived B cell lymphomas. We found that HVEM deficiency increased B cell competitiveness during pre-GC and GC responses. The immunoglobulin (Ig) superfamily protein BTLA regulated HVEM-expressing B cell responses independently of B-cell-intrinsic signaling via HVEM or BTLA. BTLA signaling into T cells through the phosphatase SHP1 reduced T cell receptor (TCR) signaling and preformed CD40 ligand mobilization to the immunological synapse, thus diminishing the help delivered to B cells. Moreover, T cell deficiency in BTLA cooperated with B cell Bcl-2 overexpression, leading to GC B cell outgrowth. These results establish that HVEM restrains the T helper signals delivered to B cells to influence GC selection outcomes, and they suggest that BTLA functions as a cell-extrinsic suppressor of GC B cell lymphomagenesis.
The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) occasionally follows subarachnoid hemorrhage (SAH). Plasma ADH level in patients with SAH mainly due to cerebral aneurysms was studied, and the risk for developing SIADH following SAH was discussed. Plasma ADH was measured using radio immunoassay in 25 control subjects and in 36 patients with SAH. Repeated plasma ADH measurements were made preoperatively in cases with SAH until 4 weeks after SAH. The mean (±SD) plasma level of ADH in control subjects was 3.8±1.2 pgml. Plasma ADH levels in cases with SIADH were 6.4±2.9 pgl, inappropriately elevated for the corresponding serum osmolarities and significantly higher than that of control subjects (P<0.001). The majority of cases with SIADH were Grade III or IV after Hunt & Hess. Even though the mean value of serum sodium or osmolarity was not significantly different from the controls, the mean plasma level of ADH in cases with Grade III or IV was significantly higher than the controls. The mean (±SD ) plasma level of ADH in cases with Grade III or IV measured within 14 days following SAH was, 7.8±2.8 pgml, significantly elevated (P<0.001). When compared with control subjects, cases with SAH did not show any significant increase of plasma aldosterone, blood urea nitrogen, and hematocrit which would have suggested blood volume depletion. Therefore, it was suggested that the excessive release of ADH recognized in the present study was due to non-physiological (inappropriate) release of ADH caused by non-osmotic factors other than blood volume depletion. From the present study, it was concluded that patients with Grade III or IV, especially in an acute stage following SAH, were unable to suppress ADH release properly and to excrete a water load normally. Therefore, these patients were susceptible to SIADH in spite of usually normal serum sodium. Thus, fluid intakes and electrolytes should be closely observed.
IL-31 receptor blockade suppresses pruritus of atopic dermatitis. However, cell-type-specific contributions of IL-31 receptor to itch, its expression mechanism, and the downstream signaling pathway to induce itch remain unknown. Here, using conditional knockout mice, we demonstrate that IL-31-induced itch requires sensory neuronal IL-31 receptor and STAT3. We find that IL-31 receptor expression is dependent on STAT3 in sensory neurons. In addition, pharmacological experiments suggest that STAT3 activation is important for the itch-inducing signaling downstream of the IL-31 receptor. A cutaneous IL-31 injection induces the nuclear accumulation of activated STAT3 first in sensory neurons that abundantly express IL-31 receptor and then in other itch-transmitting neurons. IL-31 enhances itch induced by various pruritogens including even chloroquine. Finally, pruritus associated with dermatitis is partially dependent on sensory neuronal IL-31 receptor and strongly on sensory neuronal STAT3. Thus, sensory neuronal STAT3 is essential for IL-31-induced itch and further contributes to IL-31-independent inflammatory itch.
In twenty patients with ischemic cerebrovascular disease fibrinopeptide A (FPA) and fibrinopeptide Bβ 15-42 (Bβ 15-42) were serially assayed in cerebrospinal fluid (CSF) and in plasma.After plasma FPA levels began to be elevated, it took a peak from 5th to 14th day after stroke (p<0.05), and gradually returned to control level. Bβ 15-42 levels in plasma were constantly elevated at least during first three weeks (Fig. 1). On the other hand, values of FPA in CSF were initially elevated and then reached to a peak on 15th to 21st day after stroke (p<0.01). However values of Bβ 15-42 in CSF remained at control level (Fig. 2).Suggestions of these results are as follows. Coagulation activity was accelerated following the onset of stroke with a short time lag. This delay of coagulation activity was considered to be due to the stroke progression, that is, continuous activation of thromdin in the ischemic regions. And it caused the elevation of FPA that released into the subarachnoid space crossing the broken blood-brain barrier. While fibrinolytic activity in plasma was continuously elevated, that in CSF was not influenced by stroke. The reason of this difference was not proven in our series.
