{'fraction_non_alphanumeric': 0.026734104046242775, 'fraction_numerical': 0.015895953757225433, 'mean_word_length': 5.183035714285714, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
IN THIS ISSUE

A ctivation of the PI3K signaling pathway promotes survival and proliferation of CD4 effector Th cells (Teff), whereas inhibition of PI3K is associated with CD4 FoxP3 regulatory T cell (Treg) differentiation. PI3K regulation is mediated through phosphatases, including Src homology 2 domain-containing inositol polyphosphate phosphatase (SHIP), and Locke et al. (p. 975) have observed that SHIP is a key regulator of Th17 and Treg development. PI3K signaling in Treg and Teff cells was measured by Akt phosphorylation and confirmed earlier findings that phospho-Akt levels were significantly lower in Treg vs Teff cells following TCR stimulation. The mechanism behind reduced PI3K/Akt activation was analyzed by characterizing murine SHIP / T cells. SHIP deficiency did not alter Treg anergy or suppressive function in vitro, and SHIP / Treg cells suppressed colitis as effectively as wild-type (WT) Treg in mice. Unexpectedly, SHIP / Teff cells induced less severe colitis and lower levels of systemic proinflammatory cytokines compared with WT cells. This phenotype was attributed to a defect in Th17 differentiation, possibly due to reduced IL-6-induced STAT3 phosphorylation and an increased tendency toward retinoic acidand TGF-driven Treg differentiation. Thus, SHIP appears to be critical for driving Th17 development and balancing Th17 and Treg differentiation.