Elevated CD16 expression by monocytes from patients with tumor necrosis factor receptor–associated periodic syndrome

Abstract

Objective. Tumor necrosis factor receptorassociated periodic syndrome (TRAPS) is an inherited autosomal-dominant autoinflammatory condition caused by mutations in the ectodomain of the 55-kd tumor necrosis factor (TNF) receptor superfamily 1A. Proinflammatory blood monocytes with the phenotype CD14؉,CD16؉,HLA-DR؉؉ are a major source of TNF, and the number of such monocytes is increased during infection and inflammation. The aim of this study was to investigate whether the expression of circulating CD16؉ monocytes is affected in patients with TRAPS.Methods. Peripheral blood obtained from patients with TRAPS and healthy control subjects was stained with monoclonal antibodies to detect CD14؉؉, CD16؊ monocytes and CD14؉,CD16؉ monocytes, using flow cytometry. Lipopolysaccharide-induced TNF production was measured by intracellular cytokine staining. Activation-induced shedding of CD16 was investigated by treating blood samples with phorbol myristate acetate.Results. The level of CD16 expression by CD14؉, CD16؉ monocytes, but not their absolute number, was significantly elevated in patients with TRAPS, even though the patients were not experiencing clinically overt episodes of autoinflammation at the time of sampling. These findings are similar to those for the C-reactive protein levels and erythrocyte sedimentation rates in the same patients. The enhanced level of CD16 expression by monocytes from patients with TRAPS was not attributable to a defect in activationinduced shedding of CD16. The CD14؉,CD16؉ monocytes were the predominant source of TNF in both patients and healthy control subjects.Conclusion. The level of CD16 expression by monocytes was elevated in patients with TRAPS, as a feature of the underlying constitutive inflammation status.

CD16 Regulates TRIF-Dependent TLR4 Response in Human Monocytes and Their Subsets

“…Taken together, our results also suggest CD16 in monocytes and their subset as important players in human Gram-negative sepsis. Incidentally, a role for CD16 + monocytes and the CD16-mediated signaling pathway has also been suggested in other pathologies such as autoimmune diseases and some cancers (66)(67)(68)(69). Thus, targeting CD16 may serve as means to regulate monocyte/macrophage response in a variety of diseases.…”

Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals

“…The bulk of monocytes are defined as classic monocytes and are strongly positive for surface receptor CD14 (CD14 ϩϩ CD16 Ϫ ), whereas the minor subset are referred to as inflammatory monocytes (CD14 ϩ CD16 ϩ ) because of their high capacity to express proinflammatory cytokines such as TNF-␣ (6, 62, 64, 90). Inflammatory monocytes have the ability to respond directly with antimicrobial activity, whereas the classic subset of monocytes act as scavengers, removing apoptotic cells and aiding in the resolution of inflammation (46).Normally comprising Ͻ10% of all circulating monocytes, the inflammatory subset in the peripheral blood has been shown to expand with exercise (31, 78) and is associated with various inflammatory disorders (29,30,82). Elevations in body temperature (32) and secreted levels of TNF-␣ (71) also have been correlated with inflammatory subset expansion; however, to our knowledge, no data exist relative to exertional heat stress (EHS).…”

“…Normally comprising Ͻ10% of all circulating monocytes, the inflammatory subset in the peripheral blood has been shown to expand with exercise (31, 78) and is associated with various inflammatory disorders (29,30,82). Elevations in body temperature (32) and secreted levels of TNF-␣ (71) also have been correlated with inflammatory subset expansion; however, to our knowledge, no data exist relative to exertional heat stress (EHS).…”

“…Based on differential expression of antigenic markers CD14 [part of the LPS receptor, CD14/Toll-like receptor (TLR-4)/MD-2] and CD16 (Fc␥RIII), monocytes can be divided into two phenotypically and functionally distinct subsets (82,90). The bulk of monocytes are defined as classic monocytes and are strongly positive for surface receptor CD14 (CD14 ϩϩ CD16 Ϫ ), whereas the minor subset are referred to as inflammatory monocytes (CD14 ϩ CD16 ϩ ) because of their high capacity to express proinflammatory cytokines such as TNF-␣ (6,62,64,90).…”

Resolution of Psoriasis by a Leukocyte-Targeting Bacterial Protein in a Humanized Mouse Model

“…Specifically, CD16 þ proinflammatory monocytes are increased in patients with autoimmune disease and inflammation (Fingerle et al, 1993;Baeten et al, 2000;Todd et al, 2007;Ziegler-Heitbrock, 2007;Chiu et al, 2010). To determine whether LtxA also has an effect on proinflammatory monocytes, we tested the activity of LtxA on peripheral blood, gating for CD14 þ CD16 þ monocytes.…”