BTLA-expressing CD11c antigen presenting cells in patients with active tuberculosis exhibit low capacity to stimulate T cell proliferation.

Despite past extensive studies on B and T lymphocyte attenuator (BTLA)-mediated negative regulation of T cell activation, the role of BTLA in antigen presenting cells (APCs) in patients with active pulmonary tuberculosis (ATB) remains poorly understood. Here, we demonstrate that BTLA expression on CD11c APCs increased in patients with ATB. Particularly, BTLA expression in CD11c APCs was likely associated with the attenuated stimulatory capacity on T cells (especially CD8+ T cell) proliferation. BTLA-expressing CD11c APCs showed lower antigen uptake capacity, lower CD86 expression, higher HLA-DR expression, and enhanced IL-6 secretion, compared to counterpart BTLA negative CD11c APCs in healthy controls (HC). Interestingly, BTLA-expressing CD11c APCs from ATB patients displayed lower expression of HLA-DR and less IL-6 secretion, but higher expression of CD86 than those from HC volunteers. Mixed lymphocyte reaction suggests that BTLA expression is likely associated with positive rather than conventional negative regulation of CD11c APCs stimulatory capacity. This role is impaired in ATB patients manifested by low expression of HLA-DR and low production of IL-6. This previous unappreciated role for BTLA may have implications in the prevention and treatment of patients with ATB.

Elevated serum IL-35 and increased expression of IL-35-p35 or -EBI3 in CD4(+)CD25(+) T cells in patients with active tuberculosis.

Despite the recent appreciation of interleukin 35 (IL-35) function in inflammatory diseases, little is known for IL-35 response in patients with active tuberculosis (ATB). In the current study, we demonstrated that ATB patients exhibited increases in serum IL-35 and in mRNA expression of both subunits of IL-35 (p35 and EBI3) in white blood cells and peripheral blood mononuclear cells. Consistently, anti-TB drug treatment led to reduction in serum IL-35 level and p35 or EBI3 expression. TB infection was associated with expression of p35 or EBI3 protein in CD4(+) but not CD8(+) T cells. Most p35(+)CD4(+) T cells and EBI3(+)CD4(+) T cells expressed Treg-associated marker CD25. Our findings may be important in understanding immune pathogenesis of TB. IL-35 in the blood may potentially serve as a biomarker for immune status and prognosis in TB.

BTLA associates with increased Foxp3 expression in CD4(+) T cells in dextran sulfate sodium-induced colitis.

Ulcerative colitis (UC) is an inflammatory bowel disease, and its pathogenesis involves a variety of genetic, environmental, and immunological factors such as T helper cells and their secreted cytokines. B and T lymphocyte attenuator (BTLA) is an immunoregulatory receptor that has a strong suppressive effect on T-cell function. However the role of BTLA in UC remains poorly understood. Here we demonstrated that the frequency of BTLA-expressing CD3(+) T cells, especially CD4(+) T cells, increased in blood and mucosa in mice with DSS-induced colitis. The frequency of Foxp3-expressing cells in BTLA+ CD4(+) T cell from lamina propria mononuclear cells (LPMCs) was much higher in DSS-treated mice than that in controls. Similarly, the proportion of IL-17+ cells in BTLA+ CD4(+) T cells from LPMCs in DSS-treated mice is much higher than that in controls, while no perceptible difference for the proportion of IFN-γ+ cells in BTLA+ CD4(+) T cells was noted between DSS-treated mice and controls. Treatment of mesalazine, an anti-ulcerative colitis drug, down-regulated Foxp3 and IL-17 expression in BTLA positive T cells along with attenuated severity for colitis. Our findings indicate that BTLA may be involved in the control of inflammatory responses through increasing Foxp3 expression, rather than attenuating IL-17 production, in DSS-induced colitis.

Elevated HMGB1-related interleukin-6 is associated with dynamic responses of monocytes in patients with active pulmonary tuberculosis.

There were limited studies assessing the role of HMGB1 in TB infection. In this prospective study, we aimed to assess the levels of HMGB1 in plasma or sputum from active pulmonary tuberculosis (APTB) patients positive for Mtb culture test, and to evaluate its relationship with inflammatory cytokines and innate immune cells. A total of 36 sputum Mtb culture positive APTB patients and 32 healthy volunteers (HV) were included. Differentiated THP-1 cells were treated for 6, 12 and 24 hrs with BCG at a multiplicity of infection of 10. The absolute values and percentages of white blood cells (WBC), neutrophils, lymphocytes, and monocytes were detected by an automatic blood analyzer. Levels of HMGB1, IL-6, IL-10 and TNF-α in plasma, sputum, or cell culture supernatant were measured by ELISA. The blood levels of HMGB1, IL-6, IL-10 and TNF-α, the absolute values of WBC, monocytes and neutrophils, and the percentage of monocytes were significant higher in APTB patients than those in HV groups (P < 0.05). The sputum levels of HMGB1, IL-10, and TNF-α were also significantly higher in APTB patients than those in HV groups (P < 0.05). Meanwhile, plasma level of HMGB1, IL-6, and IL-10 in APTB patients were positively correlated with those in sputum (P < 0.05), respectively. IL-6 was positively correlated with HMGB1 both in plasma and sputum of APTB patients (P < 0.05). HMGB1 and IL-6 is positively correlated with the absolute number of monocytes in APTB patients (P < 0.05). BCG induced HMGB1, IL-6, IL-10 and TNF-α production effectively in PMA-treated THP-1 cells. HMGB1 may be used as an attractive biomarker for APTB diagnosis and prognosis and may reflect the inflammatory status of monocytes in patients with APTB.

Clinicopathological features of an ascending colon mixed adenoneuroendocrine carcinoma with clinical serosal invasion.

Mixed adenoneuroendocrine carcinoma (MANEC) is exceedingly rare with a poor outcome. In this article, we reported a MANEC in a 68-year-old woman with a symptom of abdominal pain and distension. MANEC derived from the ascending colon with highly aggressive behavior. The diagnosis and distinguish of MANEC must base on histological findings and immunohistochemical findings. In this case, microscopic observation showed tumor cells were arranged in conglobate and nested by fibrous tissue with a visible cell atypia and mitotic. NEC-like and exocrine glandular cells were also been seen in a single neoplasm. MANEC tissues were immunopositive for CK, CK20, P53, CK7, CDX-2, Ki-67 (70%+), E-cad, CD56, CEA, Syn, villin and CgA, and immunonegative for CA125, NSE, ER and PR. Here, the patient was treated by surgical operation and was followed-up near 3 months, no local recurrence and distant metastasis.

Nasopharyngeal adenoid cystic carcinoma: a case report and review of the literature.

ACC derived from nasopharyngeal epithelial cells is rare, usually benign. In this article, we reported a nasopharyngeal adenoid cystic carcinoma (NACC) in a 31-year-old woman with a symptom of hoarseness, headache, epistaxis slightly, diplopia, facial numbness and dysphagia near 3 months. A tumor on the right side of the nasopharynx was confirmed by laryngoscope check and MRI of the skull base. Histopathological findings showed that tumor cells were arranged in cord-like or acinar-like by atypical hyperplastic epithelial cells forming a cribriform and tubular pattern, and immunohistochemical findings showed that tumor tissues were immunopositive for p63 (+), CK7 (+), CK19 (+), CK8 (+), CK18 (+), SMA (+), CK (+), p53 (++), S-100 (+) and Ki-67 (5%+), and negative for CD34 (-), CK5/6 (-), CEA (-) and CD117 (-). Patient was treated by surgical operation and radiotherapy, and was followed-up near 10 months, no local recurrence and distant metastasis.

BTLA exhibits immune memory for αß T cells in patients with active pulmonary tuberculosis.

Despite past extensive studies, the role of B and T lymphocyte attenuator (BTLA) in αß T cells in patients with active pulmonary tuberculosis (ATB) remains poorly understood. Here we demonstrate that BTLA expression on αß T cells is decreased in patients with M. tuberculosis (Mtb) infection. Particularly, BTLA expression levels are likely critical for αß T cells to manifest and maintain an active central memory phenotype with high capacity for secretion of IFN-γ and perforin, which are important for immune memory against TB infection. BTLA(high) αß T cells also exhibited higher capacity in response to Mtb peptide stimulation. In contrast to the role of BTLA played for negative regulation of immune responses, our data in the current studies suggest that BTLA expression on αß T cells is likely associated with protective immune memory against Mtb infection in the setting of patients with active pulmonary tuberculosis. This previous unappreciated role for BTLA may have implications for prevention and treatment of patients with Mtb infection.

Assessing the role of IL-35 in colorectal cancer progression and prognosis.

Despite the recent realization of Interleukin (IL)-35 in tumorigenesis, its exact impact on colorectal cancer (CRC) progression and prognosis, however, is yet to be elucidated clearly. We thus in the present report conducted comparative analysis of IL-35 levels between CRC patients and matched control subjects. IL-35 is highly expressed in all CRC tissues, which can be detected in vast majority of colorectal cancer cells. IL-35 levels in CRC lysates and serum samples are highly correlated to the severity of malignancy and the clinical stage of tumor. Particularly, a significant reduction for serum IL-35 was noted in patients after surgical resection, indicating that IL-35 promotes CRC progression associated with poor prognosis. Mechanistic study demonstrated a significant correlation between serum IL-35 levels and the number of peripheral regulatory T (Treg) cells in CRC patients, suggesting that IL-35 implicates in CRC pathogenesis probably by inducing Treg cells, while cancer cell-derived IL-35 may also recruit Treg cells into the tumor microenvironment in favor of tumor growth. Together, our data support that IL-35 could be a valuable biomarker for assessing CRC progression and prognosis in clinical settings.