Modulation of CD4+ T Helper Cell Memory Responses in the Human Skin

Abstract

Immunological memory is defined as the capacity to mount faster and more effective immune responses against antigenic challenges that have been previously encountered by the host. CD4+ T helper (Th) cells play central roles in the establishment of immunological memory as they assist the functions of other leukocytes. Th cells express polarized cytokine profiles and distinct migratory and seeding capacities, but also retain a certain functional plasticity that allows them to modulate their proliferation, activity, and homing behaviour upon need. Thus, in healthy individuals, T cell immunomodulation fulfils the task of eliciting protective immune responses where they are needed. At times, however, Th plasticity can lead to collateral tissue damage and progression to autoimmune diseases or, conversely, incapacity to reject malignant tissues and clear chronic infections. Furthermore, common immune players and molecular pathways of diseases can lead to different outcomes in different individuals. A mechanistic understanding of those pathways is therefore crucial for developing precise and curative medical interventions. Here, I focus on the skin microenvironment and comprehensively describe some of the cellular and molecular determinants of CD4+ T cell memory responses in homeostatic and pathological conditions. In discussing the cellular network orchestrating cutaneous immunity, I comprehensively describe the bidirectional interaction of skin antigen-presenting cells and mononuclear phagocytes with Th17 lymphocytes, and examine how the outcome of this interaction is influenced by endogenous skin molecules, including sodium salts and neuropeptides.

Heterogeneity and plasticity of tissue-resident memory T cells in skin diseases and homeostasis: a review

“…CD4 + Trm cells typically gather in lymphoid tissue, and they interact with antigen-presenting cells upon re-encounter with pathogens. However, recent investigations have revealed a significant disparity between the numbers of CD4 + and CD8 + T cells within the T-cell population residing in the skin ( 53 ). CD4 + T cells predominantly populate the dermal and epidermal compartments in humans, whereas in mouse skin, CD4 + T cells are primarily concentrated in the dermis ( 54 ).…”

“…In vitro , TGF-β upregulated the expression of CD103, and TNF-α, IL-33 and IFN-γ upregulated the expression of CD69 ( Figure 1 ). These cytokines and surface markers affect cutaneous CD4 + Trm cell tissue retention more than antigen recognition ( 53 , 60 ). CD4 + Trm cells can supersede innate immunity upon re-exposure to antigens and exert a direct effector effect.…”

In silico screening of JAK-STAT modulators from the antiviral plants of Indian traditional system of medicine with the potential to inhibit 2019 novel coronavirus

“…Hence, the modulation of these pathways will not only contribute to maintaining homeostatic regulation of the immune system but may also contribute to reducing cell apoptosis and necrosis. Other pathways involving T-helper cells, cytokine and chemokine signallers are also closely associated to enhance the immune system which could contribute to up-regulating the down-regulated immune system during corona infection [18][19][20].…”

Screening of JAK-STAT modulators from the antiviral plants of Indian traditional system of medicine with the potential to inhibit 2019 novel coronavirus using network pharmacology

“…Hence, modulation of these pathways' may contribute to the immune system's homeostatic regulation and reduce cell apoptosis and necrosis. Other pathways involving T-helper cells, cytokine, and chemokine signallers are also closely associated in enhancing the immune system that may contribute towards up-/down-regulation of the immune system during corona infection (Padovan 2017;Simon 2011;Jang et al 2005).…”