10.3 Skin-associated lymphoid tissue (SALT)

The skin is our first line of defense against pathogens and environmental threats. Skin-associated lymphoid tissue (SALT) is a complex network of immune cells and structures that work together to protect us from harm and maintain skin health.

SALT includes various cell types like keratinocytes, Langerhans cells, and T cells. These cells coordinate to detect threats, initiate immune responses, and maintain a delicate balance between protection and tolerance in the skin.

Structure and Function of Skin-Associated Lymphoid Tissue (SALT)

Structure of skin-associated lymphoid tissue

• Layers of the skin involved in SALT form protective barrier against pathogens and environmental insults
  • Epidermis outer layer composed of stratified squamous epithelium (keratinocytes)
  • Dermis underlying layer rich in connective tissue, blood vessels, and immune cells
• Cellular components of SALT work together to maintain skin immunity
  • Keratinocytes produce antimicrobial peptides and cytokines (defensins, cathelicidins)
  • Langerhans cells patrol epidermis capturing and presenting antigens
  • Dermal dendritic cells orchestrate immune responses in deeper skin layers
  • T cells including memory T cells provide rapid response to known pathogens
  • Innate lymphoid cells contribute to early defense and tissue homeostasis
• Structural features enhance barrier function and regulate immune responses
  • Tight junctions between keratinocytes prevent paracellular transport of molecules
  • Basement membrane separating epidermis and dermis regulates cell migration and signaling
• Molecular components contribute to innate and adaptive immunity
  • Antimicrobial peptides directly kill microbes and modulate immune responses (β-defensins, LL-37)
  • Cytokines and chemokines coordinate immune cell recruitment and activation (IL-1, CCL20)

Role of Langerhans cells

• Origin and location establish unique niche in skin immunity
  • Derived from embryonic precursors self-renew in epidermis
  • Reside in epidermis forming network of sentinel cells
• Antigen capture and processing initiate immune responses
  • Extend dendrites to sample antigens from environment and microbiome
  • Internalize and process antigens for presentation to T cells
• Migration to lymph nodes bridges innate and adaptive immunity
  • Activation by danger signals triggers migration out of epidermis
  • CCR7-dependent movement to lymph nodes guided by chemokine gradients
• Antigen presentation activates naive T cells
  • Express MHC class I and II molecules for antigen display
  • Present antigens to naive T cells in lymph nodes initiating adaptive responses
• Cytokine production shapes immune environment
  • Secrete IL-1β, TNF-α, and IL-12 promoting inflammation and T cell differentiation
• Tolerance induction maintains skin homeostasis
  • Can promote regulatory T cell development preventing excessive inflammation

Immune Mechanisms in Skin Health and Disease

Skin-resident memory T cells

• Generation of skin-resident memory T cells provides long-term protection
  • Develop from effector T cells after infection or vaccination creating tissue-specific immunity
• Location and retention ensure rapid response to local threats
  • Reside in epidermis and dermis strategically positioned for surveillance
  • Express CD69 and CD103 for tissue retention anchoring cells in skin
• Rapid response to pathogens enhances local immunity
  • Provide immediate protection upon re-exposure to known antigens
  • Secrete cytokines and chemokines to recruit other immune cells amplifying response
• Long-term persistence maintains protective barrier
  • Maintain protective immunity for extended periods without recirculation
• Heterogeneity allows diverse immune functions
  • Include both CD4+ and CD8+ T cell subsets with distinct roles in immunity

Immunology of skin disorders

• Psoriasis characterized by chronic inflammation and hyperproliferation
  • T cell-mediated autoimmune response targets skin antigens
  • Overproduction of IL-17 and IL-22 drives inflammatory cascade
  • Keratinocyte hyperproliferation leads to plaque formation
  • Neutrophil infiltration contributes to tissue damage
• Atopic dermatitis involves allergic inflammation and barrier dysfunction
  • Th2-driven immune response promotes allergic sensitization
  • Increased IgE production mediates hypersensitivity reactions
  • Impaired skin barrier function allows penetration of allergens and irritants
  • Overexpression of thymic stromal lymphopoietin (TSLP) promotes Th2 responses
• Common features highlight shared pathways in skin inflammation
  • Chronic inflammation persists due to dysregulated immune responses
  • Dysregulation of immune cell populations alters tissue homeostasis
  • Altered cytokine profiles drive pathological changes in skin
• Therapeutic approaches target specific immune pathways
  • Immunosuppressive drugs (corticosteroids, calcineurin inhibitors) broadly suppress inflammation
  • Biologics targeting specific cytokines or receptors (anti-TNF, anti-IL-17) offer precise intervention