P110
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta isoform also known as phosphoinositide 3-kinase (PI3K) delta isoform or p110 is an enzyme that in humans is encoded by the PIK3CD gene.
p110 regulates immune function. In contrast to the other class IA PI3Ks p110 and p110, p110 is principally expressed in leukocytes (white blood cells). Genetic and pharmacological inactivation of p110 has revealed that this enzyme is important for the function of T cells, B cell, mast cells and neutrophils. Hence, p110 is a promising target for drugs that aim to prevent or treat inflammation, autoimmunity and transplant rejection.
Phosphoinositide 3-kinases (PI3Ks) phosphorylate the 3-prime OH position of the inositol ring of inositol lipids. The class I PI3Ks display a broad phosphoinositide lipid substrate specificity and include p110, p110 and p110. p110 and p110 interact with SH2/SH3-domain-containing p85 adaptor proteins and with GTP-bound Ras.

# Biochemistry
Like the other class IA PI3Ks, p110 is a catalytic subunit, whose activity and subcellular localisation are controlled by an associated p85, p55, p50  or p85 regulatory subunit. The p55 regulatory subunit is not thought to be expressed at significant levels in immune cells. There is no evidence for selective association between p110, p110 or p110 for any particular regulatory subunit. The class IA regulatory subunits (collectively referred to here as p85) bind to proteins that have been phosphorylated on tyrosines. Tyrosine kinases often operate near the plasma membrane and hence control the recruitment of p110 to the plasma membrane where its substrate PtdIns(4,5)P2 is found. The conversion of PtdIns(4,5)P2 to PtdIns(3,4,5)P3 triggers signal transduction cascades controlled by PKB (also known as Akt), Tec family kinases and other proteins that contain PH domains. In immune cells, antigen receptors, cytokine receptors and costimulatory and accessory receptors stimulate tyrosine kinase activity and hence all have the potential to initiate PI3K signalling.

# Functions
For reasons that are not well understood, p110 appears to be activated in preference to p110 and p110 in a number of immune cells. The following is a brief summary of the role of p110 in selected leukocyte subsets.

## T cells
In T cells, the antigen receptor (TCR) and costimulatory receptors (CD28 and ICOS) are thought to be main receptors responsible for recruiting and activating p110. Genetic inactivation of p110 in mice causes T cells to be less responsive to antigen as determined by their reduced ability to proliferate and secrete interleukin 2. T cell specific deletion of p110 has revealed its role in antibody responses.
This may in part result from incomplete assembly of other signalling proteins at the immune synapse. The TCR cannot stimulate the phosphorylation of Akt in that absence of p110 activity.

## B cells
p110 is a regulator of B cell proliferation and function. p110-deficient mice have deficient antibody responses. They also lack to B cell subsets: B1 cells (found in body cavities such as the peritoneum) and marginal zone B cells, found in the periphery of spleen follicles).

## Mast cells
p110 controls mast cell release of the granules responsible for allergic reactions. Thus inhibition of p110 reduces allergic responses.

## Neutrophils
In conjunction with p110, p110 controls the release of reactive oxygen species in neutrophils.

## Denritic cells
p110 controls lipopolysaccharide induced Toll-like-receptor-4 mediated innate immune responses in dendritic cells and mice carrying an inactive p110 is susceptible to lipopolysaccharide mediated endotoxin shock.

# Activated PI3K delta syndrome
Inherited mutations in the PIK3CD gene which increase p110 catalytic activity cause a primary immunodeficiency syndrome called APDS or PASLI.

# Pharmacology
US pharmaceutical company ICOS produced a selective inhibitor of p110 called IC87114. This inhibitor selectively impairs B cell, mast cell and neutrophil functions and is therefore a potential immune-modulator.
The p110 inhibitor idelalisib was developed by Gilead Sciences. Idelalisib in combination with rituximab showed favourable progression free survival in a phase III clinical trial for chronic lymphocytic leukemia (CLL) compared with patients that received rituximab and placebo.
In July 2014 idelalisib was approved by the FDA as a treatment for CLL patients.
In September 2017 copanlisib, inhibiting predominantly p110 and p110, got FDA approval for the treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies.
In September 2018 duvelisib was approved by the FDA as a treatment for relapsed or refractory CLL, and relapsed follicular lymphoma (FL) patients, who have received at least two prior therapies.
A 2015 study found that p110 inhibitors had a side-effect of boosting mouse immune responses against multiple cancers, including both solid and hematological types. Breast cancer mice survival times nearly doubled and spread significantly less, with far fewer and smaller tumors. Post-surgical survival also improved. Subject immune systems could also develop an effective memory response, extending protection. p110 inactivation in regulatory T cells unleashes CD8+ cytotoxic T cells.

# Interactions
PIK3CD interacts with PIK3R1, and PIK3R2.