What kind of connective tissue is found in the papillary layer of the dermis?

Extracellular Matrix and Cells of the Dermis

The extracellular matrix is composed of collagens, elastins, proteoglycans, and glycoproteins. Unlike the epidermis, the dermis is relatively acellular. Despite the paucity of cells that generate the extracellular matrix, it is a highly dynamic environment and plays a central role in cell proliferation, differentiation, and migration.48 It is divided into the papillary dermis and the reticular dermis (Fig. 32.2). The papillary dermis is about twice the depth of the epidermis, approximately 300 µm, and it contains dermal papillae that interdigitate with epidermal rete pegs. The papillary dermis contains relatively fine extracellular matrix fibers and extends from the lamina densa to the upper (subpapillary) vascular plexus within the dermis. The remaining dermis (approximately 2500 µm deep), the reticular dermis, contains thicker extracellular matrix fibers.

The extracellular matrix is composed mainly of collagen, which accounts for approximately 72% of the dry weight. Of the 28 recognized types of collagen, type 1 and type 3 collagens are the most abundant in the adult dermis. Collagen molecules, each composed of three polypeptides containing the characteristic repeating Gly-X-Y amino acid triplets, are arranged in configurations designated as staggered, chicken wire–like, and antiparallel, which are intermolecularly cross-linked to produce collagen fibers. These fibers provide mechanical strength to the dermis.

A successive network of elastic fibers is part of the extracellular matrix of the dermis, accounting for approximately 4% of the dry weight. The three main types of elastic fibers are oxytalan, elaunin, and mature. They contain as much as 90% elastin, with lesser amounts of various other proteins, including fibrillin, vitronectin, decay-accelerating factor, and fibronectin. The elastic fiber network extends from the lamina densa through the dermis, with oxytalan fibers extending vertically from the DEJ to the interface between the papillary and reticular dermis and then converting to horizontally distributed elaunin fibers and to mature elastic fibers in the reticular dermis. The elastic fiber network allows the skin to return to its original shape after stretching or deformation.

Dermal collagen fibers and elastic fibers are embedded in a hydroscopic ground substance formed by large proteoglycans of approximately 100 to 2500 kD that account for up to 0.2% of the dry weight of the dermis. Each proteoglycan has a core protein (e.g., versican, decorin) with one or more covalently attached glycosaminoglycan (GAG) polysaccharides, such as chondroitin sulfate, heparan sulfate, keratan sulfate, dermatan sulfate, or hyaluronic acid, as a free GAG. Proteoglycan nomenclature depends on the core protein amino acid sequence and the identity of the disaccharide subunits forming the attached GAG(s).

Proteoglycans influence dermal volume and compressibility through their substantial capacity to bind water. They also influence dermal cell activity by binding growth factors, such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF); their receptors; and various cytokines.49 Similarly, different forms of hyaluronic acid can modulate Langerhans cell maturation and T cell activation; the high and low molecular weight forms typically are antiinflammatory and proinflammatory, respectively.50 In addition to their presence in the extracellular matrix, proteoglycans can be found intracellularly (e.g., serglycin core protein–containing proteoglycan in mast cell secretory granules) and on membrane surfaces (e.g., syndecan 2 core protein–containing proteoglycan on fibroblasts) of dermal cells. Proteoglycans also are expressed in the DEJ and epidermis of the skin. Fibronectin, thrombospondin, vitronectin, and tenascin are dermal glycoproteins (i.e., proteins glycosylated with non-GAG polysaccharides) that influence dermal cell functions such as cell activation, migration, and differentiation. For example, Langerhans cell migration involves the interaction of cellular β1 integrin with basement membrane laminin and extracellular matrix fibronectin.

Clinical Manifestations

Solitary mastocytomas are usually 1-5 cm in diameter. Lesions may be present at birth or may arise in early infancy at any site. The lesions may manifest as recurrent, evanescent wheals or bullae; in time, an infiltrated, pink, yellow, or tan, rubbery plaque develops at the site of whealing or blistering (Fig. 678.13). The surface acquires a pebbly, orange peel–like texture, and hyperpigmentation may become prominent. Stroking or trauma to the nodule may lead to urtication (Darier sign) due to local histamine release; rarely, systemic signs of histamine release become apparent.

Urticaria pigmentosa is the most common form of mastocytosis in children. In the first type of urticaria pigmentosa, theclassic infantile type, lesions may be present at birth but more often erupt in crops in the 1st several mo to 2 yr of age. New lesions seldom arise after age 3-4 yr. In some cases, early bullous or urticarial lesions fade, only to recur at the same site, ultimately becoming fixed and hyperpigmented. In others, the initial lesions are hyperpigmented. Vesiculation usually abates by 2 yr of age. Individual lesions range in size from a few millimeters to several centimeters and may be macular, papular, or nodular. They range in color from yellow-tan to chocolate brown and often have ill-defined borders (seeFig. 678.13). Larger nodular lesions, like solitary mastocytomas, may have a characteristic orange peel texture. Lesions of urticaria pigmentosa may be sparse or numerous and are often symmetrically distributed. Palms, soles, and face are sometimes spared, as are the mucous membranes. The rapid appearance of erythema and whealing in response to vigorous stroking of a lesion can usually be elicited; dermographism of intervening normal skin is also common. Affected children can have intense pruritus. Systemic signs of histamine release, such as anaphylaxis-like episodes, hypotension, syncope, headache, episodic flushing, tachycardia, wheezing, colic, and diarrhea, are uncommon and occur most frequently in the more severe types of mastocytosis. Flushing is by far the most common symptom seen.

Thesecond type of urticaria pigmentosa may begin in infancy but typically develops in adulthood. This type does not resolve, and new lesions continue to develop throughout life. It is associated with mutations in the stem cell factor gene. Patients with this type of mastocytosis are the population in whom systemic involvement may develop.

Systemic mastocytosis is marked by an abnormal increase in the number of mast cells in other than cutaneous tissues. It occurs in approximately 5–10% of patients with mutant stem cell factor–related mastocytosis and is uncommon in children. Bone lesions are often silent (but may be painful) and are detectable radiologically as osteoporotic or osteosclerotic areas, principally in the axial skeleton. Gastrointestinal tract involvement may produce complaints of abdominal pain, nausea, vomiting, diarrhea, steatorrhea, and bloating. Mucosal infiltrates may be detectable by barium studies or by small bowel biopsy. Peptic ulcers also occur. Hepatosplenomegaly due to mast cell infiltrates and fibrosis has been described, as has mast cell proliferation in lymph nodes, kidneys, periadrenal fat, and bone marrow. Abnormalities in the peripheral blood, such as anemia, leukocytosis, and eosinophilia, are noted in approximately 30% of patients. Mast cell leukemia may occur.

3.2.1.2 Dermis

Dermis, the layer under epidermis is made up of fibroblasts and creates a tough, supportive cell matrix for the skin. It is consisted of two layers; thin papillary layer attached to epidermis with thin loosely arranged of collagen fibers and a thick reticular layer containing bundles of collagen extends from the base of the papillary layer to the hypodermis. Dermal fibroblasts produce collagen fibers; structural proteoglycan and elastin which embed macrophages and immune competent mast cells; 70% of the dermis is constructed by collagen protein which maintains skin toughness and strength. Proteoglycan gives viscosity and hydration to the dermis while elastin provides normal elasticity and flexibility. Other skin components such as sweat glands, hair root, blood, and lymphatic vessels are placed within these cells and fibrous tissue. Dermis thickness varies from 0.6 mm on the eyelids to 3 mm on the back, palms, and soles.

11.6 The Dermis

Dermis, the structural foundation of skin, accounts for about 90 percent of its weight. The primary cell type in the dermis are fibroblasts, which produce the extracellular structural proteins, collagen, elastin (Figure 11.5), as well as GAGs, the major water holding components of the dermis. Together, these components form the extracellular matrix (ECM), once thought to be an inert compartment of skin, providing a structural foundation. This view of the dermis (and the ECM) has now been completely discarded (59), and the significant physical, chemical and biological roles of these components continue to be unraveled. Today, there is no debate as to the fact that true anti-aging benefits can be achieved by impacting the dermal matrix, with its abundant blood and lymph vessels, sensory and trophic neuronal components, mast cells, dendritic cells that act as sentinels of the immune system, sweat glands, and pilo-sebaceous follicles that extend into the dermis; as well as adipocytes that synthesize and store fat, impacting the skin appearance, but in addition secrete a slew of cytokines and hormones that have vast implication to human health, metabolic syndrome, obesity, and longevity.

Dermis

The dermis arises from several sources. In the trunk, dorsal dermis arises from the dermatome of the somites, whereas ventral and lateral dermis and dermis of the limbs is derived from the lateral plate mesoderm. In the face, much of the cranial skin, and anterior neck, dermal cells are descendants of cranial neural crest ectoderm (see Fig. 12.9).

Ectodermal Wnt signaling, acting through the β-catenin pathway, specifies the dermomyotomal cells, as well as mesenchymal cells of the ventral somatopleure closest to the ectoderm, to become dermal cells, which express the dermal marker, Dermo 1 (see Fig. 9.8A). The future dermis is initially represented by loosely aggregated mesenchymal cells that are highly interconnected by focal tight junctions on their cellular processes. These early dermal precursors secrete a watery intercellular matrix rich in glycogen and hyaluronic acid.

Early in the third month, the developing dermis undergoes a transition from the highly cellular embryonic form to a state characterized by the differentiation of the mesenchymal cells into fibroblasts and the formation of increasing amounts of a fibrous intercellular matrix. The principal types of fibers are types I and III collagen and elastic fibers. The dermis becomes highly vascularized, with an early capillary network transformed into layers of larger vessels. Shortly after the eighth week, sensory nerves growing into the dermis and epidermis help complete reflex arcs and thus allow the fetus to respond to pressure and stroking.

Origin, migration, and formation of the dermis

The dermis of craniofacial, dorsal trunk, ventral trunk, and limb regions originates from different mesenchymal populations that migrate to subectodermal locations. The muzzle dermis develops at E10.5 and the cranial dermis at E13.5, both from neural crest-derived cells. In contrast, the dermis over the occiput and otic regions forms from the cephalic unsegmented paraxial mesoderm. The dorsal dermis forms between E12.5 and E14 from the mesenchymal cells derived from the medial part of the somitic dermomyotome. The promotion of dermal fate occurs at different times in the back: first in its laterodorsal parts, then in the flanks, and finally above the neural tube (Figure 12.1). The limb dermis and the ventral trunk dermis form about E12.5 and E14.5, respectively, following cell migration from the lateral plate mesoderm. At this time, the corresponding ectoderm transforms into a typical embryonic epidermis (Figure 12.1: compare A1 and A3). The different mesenchymal progenitors express En-1, while Dermo1 expression is the earliest marker for dermal cells (reviewed in Atit et al., 2006). The dermis differentiates into two layers: an upper dense dermis and a lower loose dermis. Formation of an upper dense dermis indicates that dermal cells must reach a high density before they can redistribute into dermal condensations and thus participate in the formation of cutaneous appendage primordia (Olivera-Martinez et al., 2004). The upper and the lower dermis correspond to two dermal cell lineages (Driskell et al., 2013). At E14.5, hair primordia form on laterodorsal skin subsequent to—and are indicative of—dermis formation, whereas the formation of hair primordia is delayed on the flanks and even more above the neural tube (Figure 12.1C). At E16.5, the hair primordia have given rise to hair pegs on laterodorsal skin (Figure 12.1C’).