Findings highlight the important function of keratinocytes in determining the epidermal occupancy of dendritic
cells and resident memory T cells and provide a potential therapeutic target to deplete these cells in disease states.
4. LC and TGFb
TGFb1-/- mice lack LC
TGFb1 likely required by LC
precursors
TGFb1 promotes LC
differentiation in vitro
TGFb1 is required for LC
development
22. avb6/b8
KC
TGFb
R
TGFb
TGFb-LAP
Trm
TGFb
R
TGFb-LAP
LC
Model
Retention of LC and Trm in Epidermis
Epidermal retention
Epidermal retention
TGFb
Keratinocytes directly control epithelial retention of
leukocytes via a novel mechanism of intercellular
communication
• LC migration is cell extrinsic (i.e. Keratinocytes
determine LC migration)
• Avβ6 and Avβ8 are spatially distinct and regulated
• DC and T cell retention varies by epidermal anatomy
and could be differently regulated
• Targeting TGFβ or its activation could be used to deplete
TRM from epidermis (e.g. Alopecia Areata, Psoriasis,
CTCL, Vitiligo)
Mohammed et al. Nature Immunology, 2016
23. Acknowledgements
University of Minnesota
Javed Muhammed
Aleh Bobr
Nathan Welty
Brian Chicione
Sakeen Kashem
Botond Igyarto
Brian Astry
David Masopust
Lalit Beura
NIAMS Dermatology
Foundation
Sloan Kettering Cancer
Ming Li
INSERM, Lyon
Laurent Bartholin
UCSF
Dean Sheppard
NYU
Dan Rifkin
Mayo Clinic
Alina Bridges