4. Questions: Cutaneous Immune System

1. Epidermis: Keratinocytes, ECTS (mouse), LCs

2. Dermis: ydT17 cells (mostly in mouse, druing inflammation in humans), mast cells

3. Hypodermis: immunologically not so relevant, Makrophagen

Conreocytes and the formation of stratum corneum

• protective againt infection

• pathogenic (lead to unwanted inflammation, thought as kickstarters of psoriasis)

• interact witth DETCs which have key in wound healing

LCs, cDC1 and cDC2

Differences:

• location (dermis for cDCs & epidermis for LCs)

• LCs are not tailored towards specific CD4 T cell responses and do not generally cross primer like cDC1

• LC are fetal and long-lived whereas cDCs are short lived and constantly regenerated

• LC can better suvey againt barrier invasions

1. DETC

   Location: Epidermis

   TCR: Almost invariant Vγ5Vδ1

   Features: Long-lived, self-renewing, dendritic morphology

   1. Role

      • Constantly survey keratinocytes for stress ligands

      • Produce growth factors (KGF, IGF-1) → wound healing

      • Secrete cytokines (IFN-γ, TNF-α) → early defense

2. ydT17

   Location: Dermis

   TCR: More diverse (mainly Vγ4⁺, Vγ6⁺ subsets)

   Features: Enriched for IL-17 production (RORγt⁺)

   Role:

   • Produce IL-17A and IL-22

   • Recruit neutrophils, induce antimicrobial peptides in keratinocytes

   • Key in antifungal and antibacterial defense

   • Can also drive pathology (psoriasis-like inflammation)

Specialized kerationytes along the length of the hair follicle produce chemokines and cytokines that attract different immune cells and support their survival and activatio. The follicle bulge produces immunosuppressice cytokines and molecules like IL-10, TGFß1 and FASL preventing effector T cell responses creating an immune privilged site

Th17 mediated response to Propionibacterium acnes causes common acne symptoms

Neuroimmune interactions and pathological inflammation example: cross talk between sensory neurons, DCs and ydT17 cells in the IMQ model of psoriasis

Neuroimmune interactions and protective immunity example: cross-talk between sensory neurons, DCs and ydT17 cells in the Candida albicans model of infection

extracellular -> response dominated by IL-17 producing cells

innate immune system

protective T cell -> innate immune system

• pathogen like that & its components will be recognized by epithelial and innate immune cells includings DCs & PRR (pattern recoginziton receptors)

  -> trigger release of type 3 inducing cytokines

• dead epithelial will be phagocytosed by macrophages which will also release similar cytokines

• in some instances sensory neurons may also participate in instructing this cytokine reponse

• there will be activation of local typ3 innate lymphoid cells which will start producing IL 17 wich in turn will initate recruitement of innate pro-inflammatory cells like neutrophils

• migratory dcs will pick up antigen and activaated by cytokine milieu and PRRs will migrate to local skind draining LNs

• Be aware that during most infections ther will be migration of all types of DCs however depening on the pathogen induced stimuli a certain subset will often dominate. In this case cDC2, which together with the already “rich” type 3 cytokine envrionment will direct the differentiation of CD4 T cells towards the Th17 lineage.

• The same cDC2s will additionally instruct the newly generated Th17 cells to express skin-homing cheomokine receptors and adhesion meolecular in order ot migrate back to the skina fter exiting the LN.

Leishmania major infection is a good example of microbiota being important:

Hair follicle break straum corneum barrier what make it not that impenetrable